MACROCHEM CORP
S-3/A, 1997-10-24
PHARMACEUTICAL PREPARATIONS
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       As filed with the Securities and Exchange Commission on October 24, 1997
                                                      Registration No. 333-34533
================================================================================
                          SECURITIES AND EXCHANGE COMMISSION
                             WASHINGTON, D.C. 20549
                               AMENDMENT NO. 1 TO
                                    FORM S-3
    

             REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933

                              MACROCHEM CORPORATION
             (Exact name of Registrant as specified in its charter)

             DELAWARE                                         04-2744744
    (State or other jurisdiction                           (I.R.S. Employer
  of incorporation or organization)                       Identification No.)

                               110 Hartwell Avenue
                         Lexington, Massachusetts 02173
                                 (617) 862-4003
      (ADDRESS, INCLUDING ZIP CODE, AND TELEPHONE NUMBER, INCLUDING AREA CODE, 
                  OF REGISTRANT'S PRINCIPAL EXECUTIVE OFFICES)

   ALVIN J. KARLOFF                                Copy to:
   PRESIDENT AND CHIEF EXECUTIVE OFFICER           DWIGHT W. QUAYLE, ESQUIRE
   MacroChem Corporation                           ROPES & GRAY
   110 Hartwell Avenue                             One International Place
   Lexington, Massachusetts 02173                  Boston, MA  02110-2624
   (617) 862-4003                                  (617) 951-7406
 (Name, address, including zip code, and telephone number, including area code,
                              of agent for service)

Approximate date of commencement of proposed sale to the public: From time to
time after the effectiveness of the Registration Statement.

If the only securities being registered on this form are being offered pursuant
to dividend or interest reinvestment plans, please check the following box. [ ]

If any of the securities being registered on this form are to be offered on a
delayed or continuous basis pursuant to Rule 415 under the Securities Act of
1933, other than securities offered only in connection with dividend or interest
reinvestment plans, check the following box.[X]

If this form is filed to register additional securities for an offering pursuant
to Rule 462(b) under the Securities Act, please check the following box and list
the Securities Act registration statement number of the earlier effective
registration statement for the same offering. [ ]

If this form is a post-effective amendment filed pursuant to Rule 462(c) under
the Securities Act, check the following box and list the Securities Act
registration statement number of the earlier effective registration statement
for the same offering. [ ]

If delivery of the prospectus is expected to be made pursuant to Rule 434, 
please check the following box. [ ]
                                                                               
THE REGISTRANT HEREBY AMENDS THIS REGISTRATION STATEMENT ON SUCH DATE OR DATES
AS MAY BE NECESSARY TO DELAY ITS EFFECTIVE DATE UNTIL THE REGISTRANT SHALL FILE
A FURTHER AMENDMENT WHICH SPECIFICALLY STATES THAT THIS REGISTRATION STATEMENT 
SHALL THEREAFTER BECOME EFFECTIVE IN ACCORDANCE WITH SECTION 8(A) OF THE 
SECURITIES ACT OF 1933, OR UNTIL THE REGISTRATION STATEMENT SHALL BECOME 
EFFECTIVE ON SUCH DATE AS THE SECURITIES AND EXCHANGE COMMISSION, ACTING 
PURSUANT TO SAID SECTION 8(A), MAY DETERMINE.
- --------------------------------------------------------------------------------
<PAGE>
PROSPECTUS                                                SUBJECT TO COMPLETION
                                                          OCTOBER 24, 1997

                              MACROCHEM CORPORATION

                        1,186,800 Shares of Common Stock
                                -----------------

   
     All of the shares of MacroChem  Corporation,  a Delaware  corporation  (the
"Company"), Common Stock, par value $.01 per share (the "Common Stock"), offered
hereby are being sold by the  holders of the Common  Stock  named  herein  under
"Selling Stockholders" (the "Selling Stockholders").  The Common Stock is traded
on NASDAQ under the symbol  "MCHM." On September  30, 1997,  the closing bid and
ask prices of the Common Stock were $8 1/8 and $8 7/8, respectively.
    
     
     The  Company  will not  receive  any of the  proceeds  from the sale of the
Common Stock.  Any or all of such Common Stock covered by this Prospectus may be
sold,  from  time to time,  by  means  of  ordinary  brokerage  transactions  or
otherwise. See "Plan of Distribution."

   
      AN INVESTMENT IN THE SHARES OF COMMON STOCK OFFERED HEREBY IS HIGHLY
   SPECULATIVE AND IS SUITABLE ONLY FOR PERSONS WHO ARE CAPABLE OF BEARING THE
    ECONOMIC RISK OF INVESTMENT, INCLUDING THE TOTAL LOSS THEREOF. SEE "RISK
                         FACTORS" COMMENCING ON PAGE 3.
    

  THESE SECURITIES HAVE NOT BEEN APPROVED OR DISAPPROVED BY THE SECURITIES AND
  EXCHANGE COMMISSION OR ANY STATE SECURITIES COMMISSION NOR HAS THE SECURITIES
        AND EXCHANGE COMMISSION OR ANY STATE SECURITIES COMMISSION PASSED
 UPON THE ACCURACY OR ADEQUACY OF THIS PROSPECTUS. ANY REPRESENTATION TO THE 
                        CONTRARY IS A CRIMINAL OFFENSE.
                              --------------------

     The Selling Stockholders named herein, or any pledgees, donees, transferees
or other successors in interest,  directly, through agents to be designated from
time to time, or through dealers or underwriters also to be designated, may sell
the  Common  Stock  from  time  to  time  in one  or  more  transactions  in the
over-the-counter  market  and  in  negotiated  transactions,   on  terms  to  be
determined  at the time of sale.  To the extent  required,  the specific  Common
Stock to be sold, the names of the Selling Stockholders, the respective purchase
prices  and  public  offering  prices,  the names of any such  agent,  dealer or
underwriter,  and any  applicable  commissions  or  discounts  with respect to a
particular offer will be set forth in any accompanying prospectus supplement or,
if appropriate,  a  post-effective  amendment to the  Registration  Statement of
which this Prospectus is a part. See "Plan of Distribution."  By agreement,  the
Company will pay all the expenses of the registration of the Common Stock by the
Selling  Stockholders  other than  underwriting  discounts and  commissions  and
transfer taxes, if any.

     The Selling  Stockholders  and any  broker-dealers,  agents or underwriters
that participate with the Selling Stockholders in the distribution of the Common
Stock may be deemed to be  "underwriters"  within the meaning of the  Securities
Act of 1933, as amended (the "Securities Act"), and any commissions  received by
them and any profit on the resale of the Common  Stock  purchased by them may be
deemed underwriting commissions or discounts under the Securities Act.
                            ------------------------
   
                The date of this Prospectus is October 24, 1997
    

- --------------------------------------------------------------------------------
Information   contained  herein  is  subject  to  completion  or  amendment.   A
registration  statement  relating  to these  securities  has been filed with the
Securities  and Exchange  Commission.  These  securities may not be sold nor may
offers to buy be acceptable prior to the time the registration statement becomes
effective.  This  prospectus  shall  not  constitute  an  offer  to  sell or the
solicitation of an offer to buy nor shall there be any sale of these  securities
in any State in which such offer,  solicitation  or sale would be unlawful prior
to registration or qualification under the securities laws of any such State.
- --------------------------------------------------------------------------------
<PAGE>
                              AVAILABLE INFORMATION

     The Company is subject to the informational  requirements of the Securities
Exchange  Act of 1934,  as amended  (the  "Exchange  Act"),  and, in  accordance
therewith,  is required to file  periodic  reports,  proxy  materials  and other
information  with the Securities  and Exchange  Commission  (the  "Commission").
Reports,  proxy statements and other  information can be inspected and copied at
the public  reference  facilities  maintained  by the  Commission  at Room 1024,
Judiciary  Plaza,  450 Fifth Street,  N.W.,  Washington,  D.C. 20549, and at its
regional  offices  located at Suite  1400,  Citicorp  Center,  500 West  Madison
Street, Chicago,  Illinois 60661, and at Seven World Trade Center, New York, New
York  10048,  and  copies  of such  material  can be  obtained  from the  Public
Reference Section of the Commission,  450 Fifth Street, N.W.,  Washington,  D.C.
20549, at prescribed rates. In addition, the Commission maintains a web site (at
http://www.sec.gov) that contains reports, proxy and information statements, and
other  information  regarding  registrants,  including  the  Company,  that file
electronically with the Commission.

     The Company has filed with the Commission a Registration  Statement  (which
term shall include all amendments,  exhibits and schedules  thereto) on Form S-3
under the  Securities Act with respect to the securities  offered  hereby.  This
Prospectus  does not  contain  all  information  set  forth in the  Registration
Statement,  certain parts of which are omitted in accordance  with the rules and
regulations of the Commission, and to which reference is hereby made. Statements
made in this  Prospectus as to the contents of any document  referred to are not
necessarily complete.  With respect to each such document filed as an exhibit to
the Registration Statement, reference is made to the exhibit for a more complete
description  of the matter  involved,  and each such  statement  shall be deemed
qualified in its entirety by such reference.  The Registration  Statement may be
inspected at the public  reference  facilities  maintained by the  Commission at
Room 1024,  Judiciary Plaza,  450 Fifth Street,  N.W.,  Washington,  D.C. 20549.
Copies of such material can be obtained from the Public Reference Section of the
Commission at 450 Fifth Street,  N.W.,  Washington,  D.C.  20549,  at prescribed
rates. The Registration  Statement was filed  electronically with the Commission
and is available on the Commission's web site (at http://www.sec.gov).

                 INCORPORATION OF CERTAIN DOCUMENTS BY REFERENCE

     The  following  documents  filed by the  Company  with the  Commission  are
incorporated by reference in this Prospectus and made a part hereof:

   
          (i)       Annual  Report  on Form  10-K  for  the  fiscal  year  ended
                    December 31, 1996, as amended by Amendment 1 thereto filed 
                    with the Commission on October 24, 1997.
    

          (ii)      Quarterly  Reports on Form 10-Q for the quarters ended March
                    31, 1997 and June 30, 1997.

          (iii)     The  Description of the Company's  Common Stock contained in
                    its  registration  statement on Form 8-A, File No.  0-13634,
                    including  any  amendment or report filed for the purpose of
                    updating such description.

                                      (2)
<PAGE>
     All documents  subsequently filed by the Company pursuant to Section 13(a),
Section  13(c),  Section 14 and Section  15(d) of the Exchange Act (i) after the
date of filing of the Registration  Statement and prior to the  effectiveness of
the Registration  Statement and (ii) after the date of this Prospectus and prior
to the  termination  of the  offering  shall be  deemed  incorporated  herein by
reference from the date of filing of such documents.  Any statement contained in
a document  incorporated  by reference  herein shall be deemed to be modified or
superseded  for  purposes  of this  Prospectus  to the extent  that a  statement
contained  herein,  or in any other  subsequently  filed  document  that also is
incorporated by reference  herein,  modifies or supersedes  such statement.  Any
such  statement  so modified  or  superseded  shall not be deemed,  except as so
modified or superseded, to constitute a part of this Prospectus.

     The Company will provide,  upon request,  without  charge to each person to
whom a copy of this Prospectus has been  delivered,  a copy of any or all of the
documents  which  have  been  or may  be  incorporated  in  this  Prospectus  by
reference,  other than  certain  exhibits to such  documents.  Requests for such
copies should be directed to: Investor  Relations,  MacroChem  Corporation,  110
Hartwell Avenue, Lexington, Massachusetts 02173, (617) 862-4003.

                                  RISK FACTORS

     IN ADDITION TO THE OTHER INFORMATION IN THIS PROSPECTUS, THE FOLLOWING RISK
FACTORS  SHOULD BE  CONSIDERED  CAREFULLY  IN  EVALUATING  THE  COMPANY  AND ITS
BUSINESS. THIS PROSPECTUS CONTAINS FORWARD-LOOKING STATEMENTS THAT INVOLVE RISKS
AND  UNCERTAINTIES.  THE COMPANY'S ACTUAL RESULTS MAY DIFFER  SIGNIFICANTLY FROM
THE RESULTS DISCUSSED IN THE  FORWARD-LOOKING  STATEMENTS IN THIS PROSPECTUS AND
IN FORWARD-LOOKING STATEMENTS MADE FROM TIME TO TIME BY THE COMPANY ON THE BASIS
OF  MANAGEMENT'S  THEN-CURRENT  EXPECTATIONS.  FACTORS  THAT MIGHT  CAUSE SUCH A
DIFFERENCE  INCLUDE,  BUT ARE NOT LIMITED  TO,  THOSE  DISCUSSED  OR REFERRED TO
BELOW.
         
     An  investment  in the  shares of  Common  Stock  offered  hereby is highly
speculative  and is  suitable  only for  persons  who are capable of bearing the
economic  risk of  investment,  including  the  total  loss  thereof.  Prior  to
purchasing any shares of Common Stock,  prospective  investors  should carefully
consider  the  following  risk  factors,  as well as other  information  in this
Prospectus.

HISTORY OF OPERATING LOSSES; NEED FOR CONTINUED WORKING CAPITAL

     The Company has been engaged  primarily in research and  development  since
its inception in 1981 and has derived limited  revenues from the commercial sale
of its products  and  licensing  of certain  technology.  The Company has had no
revenues relating to the sale of any products currently under  development.  The
Company has incurred net losses every year since its  inception  and the Company
anticipates  that losses may continue for the  foreseeable  future.  At June 30,
1997, the Company's  accumulated  deficit was approximately  $19.9 million.  The
Company's ability to continue operations after its current capital resources are
exhausted  depends on its  ability to obtain  additional  financing  and achieve
profitable operations, as to which no assurance can be given.

     The  Company  continues  to  pursue  the   commercialization  of  its  SEPA
technology  through  discussion and  presentation of its technology to potential
licensees.  No assurance  can be given that these  discussions  will lead to any
licenses.  No  assurance  can be given that any license fees will be received by
the Company.  For the  foreseeable  future,  and until  marketing  approvals are
obtained,  and/or  license  agreements  are entered into,  if ever,  the Company
anticipates  limited  licensing  revenue and no royalties from sales of products
using SEPA for pharmaceutical purposes.


                                      (3)
<PAGE>
TECHNOLOGY UNCERTAINTY AND EARLY STAGE PRODUCT DEVELOPMENT

     Although  several  systems have been  developed  by various  pharmaceutical
companies  to enhance the  transdermal  delivery of specific  drugs,  relatively
limited  research has been  conducted in the expansion of  transdermal  delivery
systems to a wider range of  pharmaceutical  products.  Although the Company has
demonstrated  in  preclinical  and clinical  studies  that its SEPA  transdermal
compounds  may  have  applicability  with a broad  range of  drugs,  transdermal
delivery  systems are currently  marketed for only a limited number of products.
In addition,  transdermal  delivery systems used to date have often demonstrated
adverse  side  effects  for  users,   such  as  skin   irritation  and  delivery
difficulties.

     The Company's proposed products are in the early development stage, require
significant further research, development, testing and regulatory clearances and
are  subject to the risks of failure  inherent  in the  development  of products
based on innovative technologies. These risks include the possibilities that any
or all of the proposed  products  may be found to be  ineffective  or toxic,  or
otherwise may fail to receive necessary regulatory clearances; that the proposed
products,  although  effective,  may be  uneconomical  to market;  or that third
parties may market superior or equivalent products.  Due to the extended testing
and  regulatory  review  process  required  before  marketing  clearance  can be
obtained,  the Company does not expect to be able to realize  revenues  from the
sale of any drugs in the near term.

NEED FOR SIGNIFICANT PRODUCT DEVELOPMENT EFFORTS AND ADDITIONAL FINANCING

     Before the Company or any  licensees of the Company may market any products
based upon the Company's technology,  significant additional development efforts
and  substantial  preclinical  and clinical  testing will be  necessary.  Unless
substantial   additional  financing  is  obtained,  the  Company  may  not  have
sufficient  working  capital  to  complete  clinical  studies  on  any  proposed
products. No assurance can be given that the Company will be able to secure such
financing on favorable terms, if at all.

UNCERTAINTIES RELATED TO CLINICAL TRIALS

     Before obtaining  regulatory approval for the commercial sale of any of its
pharmaceutical products under development, the Company must demonstrate that the
product is safe and efficacious for use in each proposed situation.  The results
of  preclinical  studies  and early  clinical  trials may not be  predictive  of
results  that  will be  obtained  in  large-scale  testing,  and there can be no
assurance that clinical  trials of the Company's  products will  demonstrate the
safety and efficacy of its  products or will result in  marketable  products.  A
number of companies in the  pharmaceutical  industry have  suffered  significant
setbacks in advanced  clinical trials,  even after promising  results in earlier
trials.  If the Company  were unable to  demonstrate  the safety and efficacy of
certain of its products, the Company may be adversely affected.

DEPENDENCE ON THIRD PARTIES FOR COMMERCIALIZATION; NO ASSURANCE OF LICENSE 
ARRANGEMENTS

     The Company intends to rely on licensees and joint venture  arrangements to
commercialize  any products that are successfully  developed.  The resources and
attention  devoted by a  licensee  to a product  are not  within  the  Company's
control, and this can result in delays in commercialization efforts. Further, no
assurance  can be  given  that  the  Company  will  be able to  enter  into  new
collaborative arrangements or that existing or future collaborative arrangements
will be successful.

                                      (4)
<PAGE>
   
PRIOR DEVELOPMENT EFFORTS HAVE NOT GENERATED SUSTAINED REVENUES OR ANY PROFITS
    

     Since the Company's  inception in 1981, the Company has engaged in research
and  development  activities  with  respect  to a variety  of  technologies  and
products,  including  polymers for medical and industrial use, dental adhesives,
osteoporotic drugs and transdermal drug-delivery products.  Although the Company
has generated  differing levels of revenue over the last several years,  none of
the Company's products or technologies has ever generated sustained revenues and
the  Company has never had  profitable  operations.  The Company has  expended a
substantial  amount of its resources in researching  and  developing  technology
relating  to these  products  as well as in  connection  with the  research  and
development of its transdermal  delivery systems. No assurance can be given that
the Company's  development  activities with respect to its transdermal  delivery
systems  will  be  successful  or that  these  efforts,  as  well,  will  not be
eventually abandoned.

GOVERNMENT REGULATION; REGULATORY APPROVALS UNCERTAIN; DEPENDENCE ON THIRD 
PARTIES FOR FDA APPLICATION PROCESS

     The Company's  proposed products,  or products  incorporating the Company's
technology,  require  the  approval  of the U.S.  Food  and Drug  Administration
("FDA")  before  they can be marketed in the U.S.  In  addition,  approvals  are
required from health  authorities in most foreign countries before such products
can be marketed therein. To obtain FDA approval to market and sell the Company's
products,  an IND  application  must be filed  and  then a New Drug  application
("NDA") or an Abbreviated New Drug  application  ("ANDA") must be filed with the
FDA.  After the IND  application  is filed and approved and before an NDA can be
filed with the FDA, a product must undergo extensive clinical trials.

     No  assurance  can be given  that any  required  FDA or other  governmental
approval  will be granted or, if granted,  will not be  withdrawn.  Governmental
regulation  may prevent or  substantially  delay the  marketing of the Company's
proposed products,  cause the Company to undertake costly procedures and furnish
a competitive  advantage to the more  substantially  capitalized  companies with
which the Company  plans to compete.  Substantial  delays in obtaining  required
approvals from foreign regulatory authorities can also result after the relevant
applications are filed. After such approvals are obtained, further delays may be
encountered before the products become commercially available. Moreover, even if
regulatory   approval  is  granted,   such  approval  may  include   significant
limitations  on indicated  uses for which any such  products  could be mandated.
Further,   pharmaceutical  products  and  their  manufacturers  are  subject  to
continuous  review after  approval,  and later  discovery of previously  unknown
problems with a product or the manufacturing  process may result in restrictions
on such  product or the  manufacturer,  including  withdrawal  of the product or
products  from the  market.  In  addition,  the  extent of  potentially  adverse
government  regulations  that may arise  from  future  administrative  action or
legislation cannot be predicted and could delay or prevent  regulatory  approval
of the Company's potential products.

     In addition to the product-specific regulation specified above, the Company
is also  subject  to  regulation  under  federal,  state and  local  regulations
regarding  work  place  safety,   environmental  protection  and  hazardous  and
controlled  substance  controls,  among others.  Non-compliance  with applicable
regulations and requirements  can result in fines and other  judicially  imposed
sanctions  including  recalls  and  criminal  prosecutions  based  on  products,
promotional  practices,   or  manufacturing  practices  that  violate  statutory
requirements. In addition, administrative remedies can involve voluntary recalls
or cessation  of sale of  products,  administrative  detention,  public  notice,
voluntary changes in labeling,  manufacturing or promotional practices,  as well
as refusal of the government to approve NDAs.

                                      (5)
<PAGE>
LACK OF MARKETING EXPERIENCE; DEPENDENCE ON THIRD PARTIES FOR MARKETING AND 
DISTRIBUTION OF PRODUCTS

     The Company intends to market and distribute its proposed  products through
others  pursuant  to  licensing,   joint  venture,   or  similar   collaborative
arrangements  or  distribution  agreements.  The  Company  has no sales force or
marketing  organization.  If the Company  directly markets and sells any of such
products,  it will, among other things,  have to attract and retain qualified or
experienced  marketing and sales  personnel.  No assurance can be given that the
Company will be able to attract and retain  qualified or  experienced  marketing
and sales  personnel or that any efforts  undertaken by such  personnel  will be
successful.  Any  contractual  arrangements  with others may result in a lack of
control  by the  Company  over  any or all of the  marketing  and  sales of such
products.

DEPENDENCE ON THIRD PARTIES FOR MANUFACTURING

     The Company currently does not have facilities capable of manufacturing any
proposed  products in commercial  quantities.  Accordingly,  the Company expects
that it will be  dependent  to a  significant  extent  on  licensees,  corporate
partners or contract  manufacturers  for such  manufacturing  and for compliance
with regulatory  requirements for good  manufacturing  practices.  The Company's
dependence on third parties for manufacturing may adversely affect the Company's
ability to develop and deliver  products on a timely and  competitive  basis. If
the Company decides to establish a commercial  manufacturing  facility,  it will
require  substantial  additional  funds,  will be  required  to hire and  retain
significant  additional  personnel and will be required to comply with extensive
governmental  regulations.  No  assurance  can be given that the Company will be
able to obtain additional capital to conduct such activities directly.

RELIANCE ON KEY EMPLOYEES; LIMITED PERSONNEL; ABILITY TO ATTRACT AND RETAIN 
QUALIFIED SCIENTISTS

     The success of the Company is dependent on the efforts and abilities of Dr.
Carlos  M.  Samour,  its  Chairman  of the  Board of  Directors  and  Scientific
Director,  Alvin J. Karloff,  its Chief Executive  Officer and President and Dr.
Stephen J. Riggi, its Vice President of Operations.  Dr. Samour, Mr. Karloff and
Dr. Riggi are employed by the Company under  employment  agreements  that are of
indefinite length and include non-disclosure and non-competition provisions. The
loss of Dr.  Samour,  Mr.  Karloff or Dr.  Riggi  could have a material  adverse
effect on the Company's business.

     The  Company's  business  also  depends  on  access to  scientific  talent,
competition  for which is intense and can be expected to  increase.  There is no
assurance  that the Company will be able to retain its existing  personnel or to
attract additional qualified employees.

   
COMPETITION WITH FIRMS WITH GREATER RESOURCES; COMPETING DRUG-DELIVERY FORMS AND
RELATED TECHNOLOGIES
    

     The  Company  competes  with  numerous  firms,  many of  which  are  large,
multi-national  organizations with worldwide  distribution.  Most of these firms
have  substantially  greater  capital  resources,  research and  development and
technical staffs,  facilities and experience in obtaining regulatory  approvals,
as well as in  manufacturing,  marketing and distribution of products,  than the
Company. The Company also competes with numerous smaller companies that may have
greater financial and other resources than the Company and increased flexibility
in developing potential products on an accelerated basis. Also, recent trends in
this area are toward further market consolidation of large drug companies into a
smaller  number  of  very  large  entities,   further  concentrating  financial,
technical  and  market  strength  and  increasing  competitive  pressure  in the
industry.  Academic  institutions,  hospitals,  governmental  agencies and other
public and private  research  organizations  are also  conducting  research  and
seeking patent protection and may develop competing  products or technologies of
their own through joint ventures or other arrangements.
                                      (6)
<PAGE>
     The  Company's   proposed  products  and  technology   compete  with  other
drug-delivery  forms  such  as oral  administration,  injection  and  continuous
infusion.  The Company  expects that  competition in the field of  drug-delivery
will increase substantially in the future. New drugs, new therapeutic approaches
or  future  developments  in  alternative  drug-delivery  technologies,  such as
time-release  capsules,  liposomes and implants, may provide therapeutic or cost
advantages  for  competitive  products.  Changes  in  transdermal  drug-delivery
technology will require  substantial  investments by companies to maintain their
competitive position and may provide  opportunities for new competitors to enter
the industry.  No assurance can be given that the Company's competitors will not
succeed in developing  technologies and products that are more effective or less
costly to use than any that are currently being developed by the Company or that
developments  by others  will not render the  Company's  potential  products  or
technologies non-competitive or obsolete.

   
UNCERTAINTY OF PROTECTION OF PATENTS AND PROPRIETARY INFORMATION;  COSTS OF
ENFORCEMENT AND INFRINGEMENT;  RELIANCE ON UNPATENTED PROPRIETARY TECHNOLOGY
    

     The Company believes that patent protection of its technologies,  processes
and products is important to its future operations. The success of the Company's
proposed  products may depend,  in part,  upon the  Company's  ability to obtain
patent  protection.  No  assurance  can be  given  that  litigation  will not be
commenced to challenge the Company's existing patents or any patents applied for
in the future,  or that the Company  would be  successful  in defending any such
challenge. In addition, no assurance can be given that the scope and validity of
the  Company's  patents will prevent third  parties from  developing  similar or
competing  products.  The  expenses  involved  in  litigation  regarding  patent
protection can be significant and cannot be estimated by the Company.  Also, the
cost of enforcing the Company's patent rights in lawsuits, if necessary,  may be
significant and could interfere with the Company's operations.

     Although the Company  intends to file  additional  patent  applications  as
management   believes   appropriate   with   respect  to  any  new  products  or
technological  developments,  no  assurance  can be given  that  any  additional
patents  will be issued  or, if  issued,  will be of  commercial  benefit to the
Company. In addition, to anticipate the breadth or degree of protection that any
such patents may afford is impossible.

     The  Company's  employees  and others who perform  research for the Company
have signed  non-disclosure and confidentiality  agreements with the Company. To
the extent that the Company  relies on  unpatented  proprietary  technology,  no
assurance  can be given that  others  will not  independently  develop or obtain
substantially  equivalent or superior technology or otherwise gain access to the
Company's trade secrets,  that any obligation of confidentiality will be honored
or that  the  Company  will  be  able  to  effectively  protect  its  rights  to
proprietary  technology.  Further,  no assurance  can be given that any products
developed  by the Company will not  infringe  patents  held by third  parties or
that,  in such case,  licenses  from such third  parties  would be  available on
commercially acceptable terms, if at all.

   
RISKS OF PRODUCT  LIABILITY  CLAIMS;  LACK OF PRODUCT  LIABILITY  INSURANCE;  
EXPENSE AND  DIFFICULTY  OF OBTAINING ADEQUATE INSURANCE COVERAGE
    
     The design,  development,  manufacture  and sale of the Company's  products
involve an inherent risk of liability claims and associated  adverse  publicity.
The Company  currently has  liability  insurance to cover claims that may result
from clinical trials, but does not maintain product liability  insurance and may
need to acquire such insurance coverage prior to the commercial  introduction of
its  products.  No  assurance  can be given  that  the  coverage  limits  of the
Company's  insurance  policies  will be adequate.  Such  insurance is expensive,
difficult to obtain and may not be available in the future on  acceptable  terms
or at all. A successful claim brought against the Company if it is uninsured, or
which is in excess of the Company's  insurance  coverage,  if any,  could have a
material adverse effect upon the Company and its financial condition.
                                      (7)
<PAGE>
UNCERTAINTY OF PHARMACEUTICAL PRICING AND RELATED MATTERS

     The future revenues and  profitability  of, and availability of capital for
bio-medical  and  pharmaceutical  companies  may be affected  by the  continuing
efforts of governmental and third-party payors to contain or reduce the costs of
health care through  various means.  For example,  in certain  foreign  markets,
pricing  or  profitability  of  prescription   pharmaceuticals   is  subject  to
government  control  and to reform in the  health  care  system.  In the  United
States,  there have been,  and the Company  expects there will continue to be, a
number of federal and state proposals to implement similar  government  control.
While the Company  cannot  predict  whether any such  legislative  or regulatory
proposals will be adopted,  the announcement or adoption of such proposals could
have a material adverse effect on the Company's prospects. If the Company or one
of its partners  succeeded in bringing one or more of its  products,  based upon
the  Company's  technology,  to  market,  there can be no  assurance  that these
products will be cost effective and that  reimbursement  to the consumer will be
available  or will be  sufficient  to allow the Company or its  partners to sell
such products on a profitable basis.

NO DIVIDENDS

     The Company has paid no dividends on its Common Stock to date and currently
intends to retain its earnings, if any, to finance its business.

POSSIBLE ISSUANCE OF PREFERRED STOCK

     The Company is  authorized  to issue up to  6,000,000  shares of  Preferred
Stock, $.01 par value (the "Preferred Stock"). The Preferred Stock may be issued
in one or more  series,  the  terms of which  may be  determined  at the time of
issuance by the Board of  Directors of the Company,  without  further  action by
stockholders.  The terms of any series of  Preferred  Stock,  which may  include
special  voting  rights  (including  the right to vote as a series on particular
matters), preferences as to dividends and liquidation, conversion and redemption
rights and sinking fund  provisions,  could  adversely  affect the rights of the
holders of the Common Stock. The issuance of such Preferred Stock could make the
possible  takeover of the Company or the  removal of  management  of the Company
more  difficult,  discourage  hostile  bids for  control of the Company in which
stockholders  may receive  premiums for their  Shares,  or otherwise  dilute the
rights of holders of Common Stock.

   
SHARES ELIGIBLE FOR FUTURE SALE;  POSSIBLE  ADVERSE EFFECTS OF OUTSTANDING  
OPTIONS AND WARRANTS ON PRICE OF COMMON STOCK

     Substantially  all of the  Company's  16,338,375  shares  of  Common  Stock
outstanding as of September 30, 1997 are freely  tradeable  pursuant to Rule 144
or otherwise.  In addition,  9,463,525  shares of Common Stock issuable upon the
exercise of the Company's  options and warrants  outstanding as of September 30,
1997 will be freely tradeable upon exercise.  An additional  1,771,455 shares of
Common Stock are  reserved for grants of options and other awards to  employees,
officers,  directors and consultants  under the Company's 1994 Equity  Incentive
Plan.
    


                                      (8)
<PAGE>

     The existence of outstanding  options and warrants for the Company's Common
Stock may affect the price at which the Common  Stock may be sold.  In addition,
the exercise of any such  options or warrants  may dilute the net tangible  book
value of the Common  Stock,  and the holders of such  options and  warrants  may
exercise  them at a time  when the  Company  would  otherwise  be able to obtain
additional equity capital on terms more favorable to the Company.

   
DISCOURAGING EFFECT OF DELAWARE ANTI-TAKEOVER LAW ON POTENTIAL AQUIRERS OF THE
COMPANY
    

     The Company, a Delaware corporation,  is subject to the General Corporation
Law of the State of  Delaware,  including  Section  203,  an  anti-takeover  law
enacted in 1988. In general,  the law restricts the ability of a public Delaware
corporation  from  engaging  in a  "business  combination"  with an  "interested
stockholder"  for a period of three years after the date of the  transaction  in
which  the  person  became an  interested  stockholder.  As a result,  potential
acquirers  of the  Company  may be  discouraged  from  attempting  to  effect an
acquisition transaction with the Company,  thereby possibly depriving holders of
shares of the Common Stock of certain opportunities to sell or otherwise dispose
of such shares at above-market prices pursuant to such transactions.

                                   THE COMPANY

     The Company was  organized  and  commenced  operations  as a  Massachusetts
corporation in 1981 and was reincorporated as a Delaware  corporation on May 26,
1992. Since the Company's inception,  it has engaged in research and development
with respect to  technologies  and products  including  polymers for medical and
industrial use, dental adhesives and transdermal drug delivery  products.  Since
1988,  the Company  has devoted a  substantial  amount of its  resources  to the
development  and licensing of the Company's  technology  for the  enhancement of
transdermal drug delivery,  SEPA(R).  The Company's  principal executive offices
are located at 110 Hartwell Avenue, Lexington, MA 02173 and its telephone number
is (617) 862-4003.
                                 
                                USE OF PROCEEDS

     The  Company  will not  receive  any of the  proceeds  of the Common  Stock
offered hereby by the Selling Stockholders.

                                      (9)
<PAGE>

                              SELLING STOCKHOLDERS

   
     The following table sets forth certain  information  regarding ownership of
the Company's Common Stock as of September 30, 1997 by the Selling Stockholders,
including  the number  and  percentage  of shares of the Common  Stock that each
Selling  Stockholder  would own beneficially if all of the shares offered hereby
by such Selling Stockholder were sold. However, because the Selling Stockholders
may sell all or part of the  Common  Stock  offered  hereby  by each of them and
because their offering is not being  underwritten on a firm commitment basis, no
estimate can be given as to the actual  amount or percentage of the Common Stock
that will be held by Selling Stockholders upon termination of this offering.

                               Number         Number     Number and Percentage
                               of Shares      of Shares  of Shares Beneficially
Selling                        Beneficially   Offered    Owned if all the Shares
Stockholder                    Owned          Hereby     Offered Hereby are Sold
- -----------                    ------------   ---------  -----------------------

                                                            NUMBER:  PERCENTAGE:
                                                           --------  ----------

Emin Company, L.L.C.(1)         1,010,102    1,000,000        10,102      *
45 Park Place South
Suite 103
Morristown, New Jersey 07960

Janssen-Meyers 
 Associates, L.P.(2)               66,558       66,558             0      *
17 State Street
New York, NY 10004

Peter Janssen(3)                1,736,396       69,729     1,666,667    9.3%
1780 Route 106
Muttontown, NY 11791

Bruce Meyers(3)                 1,220,395       69,729     1,150,666    6.6%
315 E. 86th Street
New York, NY 10028

Jacqueline M. Goode(4)              6,342        6,342             0      *
444 Storm Street
Oceanside, NY 11572

Lehman Brothers Inc.(5)            16,000       16,000             0      *
3 World Financial Center
New York, NY 10285

J. Peter Lynch(6)                  62,500       25,000        37,500      *
407 Pound Ridge Road
South Salem, NY 10590

- ----------------------------------
* Less than 1%.
    


                                      (10)
<PAGE>
(1) Emin Company,  L.L.C.  ("Emin") currently has two members,  David H. Russell
and Peter G.  Martin.  The shares of Common  Stock  offered  hereby by Emin were
issued by the Company to Mr. Russell in a private placement in 1995. Mr. Russell
contributed  the shares to the capital of Emin in July 1996. In connection  with
his purchase in the private  placement,  Mr.  Russell had the right to designate
one person to be  nominated  by the Company to serve on its Board of  Directors.
Mr. Russell  designated Mr.  Martin,  who was elected to the Company's  Board of
Directors in 1995 and re-elected in 1996 and 1997.

   
(2) The shares of Common Stock offered hereby by Janssen-Meyers Associates, L.P.
("Janssen-Meyers")  are issuable upon exercise of a warrant (the "Janssen-Meyers
Warrant") issued by the Company to  Janssen-Meyers in June 1996 for the purchase
of 145,800  shares of Common  Stock at a price of $6.075  per share.  The market
price of the Common  Stock on the grant date of the  Janssen-Meyers  Warrant was
$5.125  per share  which  resulted  in  compensation  expense  of  approximately
$433,100  being  recorded by the  Company.  The  Janssen-Meyers  Warrant,  which
expires on June 17, 1999, was issued in connection  with services  performed for
the Company by Janssen-Meyers.  In January 1997, a portion of the Janssen-Meyers
Warrant was transferred as follows:  Peter Janssen,  warrants to purchase 36,450
shares;  Bruce Meyers,  warrants to purchase  36,450  shares;  and Jacqueline M.
Goode,  warrants to purchase  6,342 shares.  Pursuant to a consulting  agreement
dated July 27,  1995,  which  expired on March 27,  1996,  the  Company  engaged
Janssen-Meyers to perform consulting  services relating to corporate finance and
other financial service matters, for which Janssen-Meyers was compensated $5,000
per  month  plus   pre-approved   expenses.   In  addition,   the  Company  paid
Janssen-Meyers  a monthly  fee of $5,000 for  consulting  services  relating  to
public relations from December 1996 through April 1997.
    

   
(3) Peter Janssen and Bruce Meyers each own 50% of  Janssen-Meyers  and each has
voting and dispositive power over 50% of the shares of Common Stock beneficially
owned by  Janssen-Meyers.  The  shares of  Common  Stock  offered  hereby by Mr.
Janssen and Mr. Meyers include  36,450 shares and 36,450  shares,  respectively,
issuable upon exercise of the portion of the Janssen-Meyers  Warrant transferred
to them and  33,279  shares  and  33,279  shares,  respectively,  issuable  upon
exercise  of the  portion  of the  Janssen-Meyers  Warrant  not  transferred  by
Janssen-Meyers  as described in footnote (2) above. In addition to these shares,
the amount listed under "Number of Shares  Beneficially  Owned" for Mr.  Janssen
includes  80,000  shares of  outstanding  Common Stock and  1,586,667  shares of
Common Stock issuable upon exercise of 52,500 Class A warrants,  55,000 Class AA
warants and 29 7/12 Unit Purchase Options (each Unit consisting of 30,000 shares
of Common Stock,  10,000 Class A warrants and 10,000 Class AA warrants) owned by
Mr.  Janssen.  The  amount  listed  for Mr.  Meyers  includes  9,000  shares  of
outstanding  Common Stock and  1,141,666  shares of Common Stock  issuable  upon
exercise  of 95,833  Class A  warrants,  95,833  Class AA  warrants  and 19 Unit
Purchase Options owned by Mr. Meyers.
    

(4) Jacqueline M. Goode was the Chief Operating Officer of  Janssen-Meyers  from
December  1994 through  March 1997.  The shares of Common  Stock  offered by Ms.
Goode are issuable  upon  exercise of the warrant  issued to her  referenced  in
footnote (2)above.

(5)  Pursuant to an agreement  dated June 5, 1997,  the Company  engaged  Lehman
Brothers Inc.  ("Lehman") to perform  consulting  services relating to corporate
finance and strategic  development matters, for which Lehman received the 16,000
shares of Common Stock offered  hereby.  In addition,  the Company has agreed to
reimburse  Lehman up to $25,000 for reasonable  expenses  incurred in connection
with  Lehman's  services  under the  agreement  and may retain Lehman to perform
investment banking services for additional  compensation.  The agreement expires
on June 5, 1998.

(6) The shares of Common Stock offered  hereby by J. Peter Lynch were granted to
him by the Company in August 1997 as compensation for consulting services.
                                      (11)
<PAGE>
                              PLAN OF DISTRIBUTION

     The  Company  will not  receive  any of the  proceeds  from the sale by the
Selling  Stockholders  of the Common  Stock  offered  hereby.  Any or all of the
shares  of  Common  Stock  may be  sold  from  time to  time  (i) to or  through
underwriters or dealers,  (ii) directly to one or more other  purchasers,  (iii)
through  agents on a  best-efforts  basis,  or (iv) through a combination of any
such methods of sale.

     The shares of the Common Stock  offered  hereby (the  "Shares") may be sold
from  time  to  time  by  the  Selling  Stockholders,  or by  pledgees,  donees,
transferees  or other  successors in interest.  Such sales may be made in one or
more transactions in the over-the-counter  market, or otherwise at prices and at
terms then  prevailing or at prices related to the then current market price, or
in  negotiated  transactions.  The  Shares  may be  sold  by one or  more of the
following:  (a) a block  trade in which the  broker or  dealer so  engaged  will
attempt to sell the Shares as agent but may position and resell a portion of the
block as principal to facilitate the  transaction;  (b) purchases by a broker or
dealer as principal and resale by such broker or dealer for its account pursuant
to this Prospectus;  and (c) ordinary brokerage transactions and transactions in
which the broker solicits  purchasers.  In effecting  sales,  brokers or dealers
engaged by the Selling  Stockholders may arrange for other brokers or dealers to
participate.  Brokers or dealers will  receive  commissions  or  discounts  from
Selling Stockholders in amounts to be negotiated prior to the sale. In addition,
any  securities  covered by this  Prospectus  which qualify for sale pursuant to
Rule 144 may be sold under Rule 144 rather than pursuant to this Prospectus.

     The Selling Stockholders and any such underwriters,  dealers or agents that
participate  in the  distribution  of the  Common  Stock  may  be  deemed  to be
underwriters  within the meaning of the  Securities  Act,  and any profit on the
sale of the Common Stock by them and any  discounts,  commissions or concessions
received by them from the Selling  Stockholders may be deemed to be underwriting
discounts and commissions under the Securities Act. The Common Stock may be sold
from time to time in one or more  transactions at a fixed offering price,  which
may be  changed,  or at  varying  prices  determined  at the  time of sale or at
negotiated prices. Such prices will be determined by the Selling Stockholders or
by an agreement  between the Selling  Stockholders  and underwriters or dealers.
Brokers  or  dealers  acting  in  connection  with  the  sale  of  Common  Stock
contemplated  by this  Prospectus  may receive fees or commissions in connection
therewith.

     At the time a  particular  offer of  Common  Stock is made,  to the  extent
required,  a  supplement  to this  Prospectus  will be  distributed  which  will
identify  and set forth the  aggregate  number of shares of Common  Stock  being
offered  and the  terms  of the  offering,  including  the  name or names of any
underwriters,  dealers or agents, the purchase price paid by any underwriter for
Common Stock purchased from the Selling Stockholders, any discounts, commissions
and other items constituting  compensation from the Selling  Stockholders and/or
the Company and any discounts,  commissions or concessions  allowed or reallowed
or paid to dealers,  including the proposed  selling  price to the public.  Such
supplement to this Prospectus and, if necessary,  a post-effective  amendment to
the  Registration  Statement of which this  Prospectus is a part,  will be filed
with the  Commission to reflect the  disclosure of additional  information  with
respect to the distribution of the Common Stock.



                                      (12)
<PAGE>

     Under applicable  rules and regulations  under the Exchange Act, any person
engaged  in  a  distribution   of  the  Common  Stock  may  be  prohibited  from
simultaneously  engaging in market making  activities with respect to the Common
Stock  for a  restricted  period  that  commences  one  or  five  business  days
(depending  upon the worldwide  average daily trading volume of the Common Stock
and the  public  float  value of the  Company)  before the day of pricing of the
Common  Stock and  continues  until the  distribution  is over.  In addition and
without  limiting  the  foregoing,  the  Selling  Stockholders  and  any  person
participating  in the  distribution  of the  Common  Stock  will be  subject  to
applicable  provisions  of the  Exchange  Act  and  the  rules  and  regulations
thereunder,  including  without  limitation  Rules 102 and 104 of  Regulation M,
which  provisions  may limit the timing of bids for and  purchases of the Common
Stock by the Selling Stockholders or any such other person.

     In order to comply with certain states' securities laws, if applicable, the
Common  Stock must be sold in such  jurisdictions  only  through  registered  or
licensed brokers or dealers.  In certain states the Common Stock may not be sold
unless its has been registered or qualified for sale in such state, or unless an
exemption from registration or qualification is available.

                                  LEGAL MATTERS

     The  validity of the shares of Common  Stock being  offered  hereby will be
passed upon for the Company by Ropes & Gray, Boston, Massachusetts.

                                     EXPERTS


     The financial statements  incorporated in this Prospectus by reference from
the Company's  Annual Report on Form 10-K for the fiscal year ended December 31,
1996 have been audited by Deloitte & Touche LLP, independent auditors, as stated
in their report,  which is  incorporated  herein by reference,  and have been so
incorporated in reliance upon the report of such firm given upon their authority
as experts in accounting and auditing.





                                      (13)
<PAGE>
=============================================  =================================
     NO DEALER, SALES PERSON OR OTHER           1,186,800 Shares of Common Stock
INDIVIDUAL HAS BEEN AUTHORIZED TO GIVE
ANY INFORMATION OR MAKE ANY
REPRESENTATIONS IN CONNECTION WITH THIS              MACROCHEM CORPORATION
OFFERING OTHER THAN THOSE CONTAINED IN THIS 
PROSPECTUS AND, IF GIVEN OR MADE, SUCH 
INFORMATION OR REPRESENTATIONS MUST NOT 
BE RELIED UPON AS HAVING BEEN AUTHORIZED 
BY THE COMPANY, THE SELLING STOCKHOLDERS
SET FORTH UNDER "SELLING STOCKHOLDERS" OR 
ANY UNDERWRITER. THIS PROSPECTUS DOES 
NOT CONSTITUTE AN OFFER TO SELL, OR A 
SOLICITATION OF ANY OFFER TO BUY ANY OF THE 
SECURITIES IN ANY JURISDICTION WHERE, OR TO 
ANY PERSON TO WHOM, IT IS UNLAWFUL TO 
MAKE SUCH OFFER OR SOLICITATION. THE 
DELIVERY OF THIS PROSPECTUS AT ANY TIME 
DOES NOT IMPLY THAT INFORMATION HEREIN IS 
CORRECT AS OF ANY TIME SUBSEQUENT TO ITS 
DATE.
                                                        October __, 1997

             -----------

          TABLE OF CONTENTS

                                       Page

Available Information . . . . . . . . .   2
Incorporation of Certain Documents
  by Reference. . . . . . . . . . . . .   2
Risk Factors. . . . . . . . . . . . . .   3
The Company . . . . . . . . . . . . . .   9
Use of Proceeds . . . . . . . . . . . .   9
Selling Stockholders. . . . . . . . . .  10
Plan of Distribution. . . . . . . . . .  12
Legal Matters . . . . . . . . . . . . .  13
Experts . . . . . . . . . . . . . . . .  13

=============================================  =================================

                                      (14)
<PAGE>
                                     PART II

                     INFORMATION NOT REQUIRED IN PROSPECTUS


ITEM 14.   OTHER EXPENSES OF ISSUANCE AND DISTRIBUTION

     The following is an itemization of the expenses  incurred or expected to be
incurred  by the  Company in  connection  with the  offering  described  in this
Registration  Statement. No portion of such expenses are expected to be borne by
Selling  Stockholders.  (Items marked with an asterisk (*)  represent  estimated
expenses):

           Registration Fee.....................................$  1,866
           Printing Cost*.......................................$    500
           Legal Fees*..........................................$ 20,000
           Accounting Fees*.....................................$  7,000
           Miscellaneous*.......................................$  1,000

                 TOTAL*.........................................$ 30,366
                                                                 =======

ITEM 15.  INDEMNIFICATION OF OFFICERS AND DIRECTORS

     Delaware General Corporation Law, Section 102(b)(7),  enables a corporation
in its original  certificate of  incorporation  or an amendment  thereto validly
approved by stockholders to eliminate or limit personal  liability of members of
its Board of Directors for  violations of a director's  fiduciary  duty of care.
However,  the  elimination or limitation  shall not apply where there has been a
breach of duty of loyalty, failure to act in good faith, engaging in intentional
misconduct or knowingly  violating a law, paying a dividend or approving a stock
repurchase that is deemed illegal or obtaining an improper personal benefit. The
Company's Certificate of Incorporation includes the following language:

     "To the  maximum  extent  permitted  by Section  102(b)(7)  of the  General
Corporation  Law of  Delaware,  a  director  of this  Corporation  shall  not be
personally  liable to the Corporation or its  stockholders  for monetary damages
for breach of fiduciary  duty as a director,  except for  liability  (i) for any
breach of the director's duty of loyalty to the Corporation or its stockholders,
(ii) for acts or  omissions  not in good  faith  or  which  involve  intentional
misconduct  or a  knowing  violation  of law,  (iii)  under  Section  174 of the
Delaware  General  Corporation  Law, or (iv) for any transaction  from which the
director derived an improper personal benefit."

     Delaware  General  Corporation  Law,  Section  145,  permits a  corporation
organized under Delaware law to indemnify directors and officers with respect to
any matter in which the director or officer  acted in good faith and in a manner
he reasonably  believed to be not opposed to the best  interests of the Company,
and, with respect to any criminal  action,  had reasonable  cause to believe his
conduct was lawful. The Bylaws of the Company include the following provisions:



                                      (15)
<PAGE>
     "Reference is made to Section 145 and any other relevant  provisions of the
General Corporation Law of the State of Delaware.  Particular  reference is made
to  the  class  of  persons,  hereinafter  called  "Indemnitees",   who  may  be
indemnified by a Delaware corporation pursuant to the provisions of such Section
145, namely,  any person,  or the heirs,  executors,  or  administrators of such
person,  who  was or is a party  or is  threatened  to be  made a  party  to any
threatened,  pending or completed  action,  suit, or proceeding,  whether civil,
criminal,  administrative,  or  investigative,  by  reason of the fact that such
person is or was a director,  officer, employee, or agent of such corporation or
is or was serving at the  request of such  corporation  as a director,  officer,
employee,  or agent of such  corporation  or is or was serving at the request of
such  corporation  as  a  director,  officer,  employee,  or  agent  of  another
corporation,  partnership,  joint  venture,  trust,  or  other  enterprise.  The
Corporation  shall, and is hereby  obligated to, indemnify the Indemnitees,  and
each of them, in each and every  situation where the Corporation is obligated to
make such indemnification  pursuant to the aforesaid statutory  provisions.  The
Corporation shall indemnify the Indemnitees, and each of them, in each and every
situation where, under the aforesaid  statutory  provisions,  the Corporation is
not  obligated,  but is  nevertheless  permitted  or  empowered,  to  make  such
indemnification,  it being understood that,  before making such  indemnification
with respect to any situation  covered under this sentence,  (i) the Corporation
shall  promptly make or cause to be made,  by any of the methods  referred to in
Subsection  (d)  of  such  Section  145,  a  determination  as to  whether  such
Indemnitee acted in good faith and in a manner he reasonably  believed to be in,
or not opposed to, the best  interests of the  Corporation,  and, in the case of
any criminal action or proceeding,  had no reasonable  cause to believe that his
conduct was unlawful, and (ii) that no such indemnification shall be made unless
it is  determined  that such  Indemnitee  acted in good faith and in a manner he
reasonably  believed  to be in, or not  opposed  to, the best  interests  of the
Corporation,  and,  in the case of any  criminal  action or  proceeding,  had no
reasonable cause to believe that his conduct was unlawful."

ITEM 16.  EXHIBITS

   
     The following exhibits are filed as part of this Registration Statement:

 Exhibit
   NO.          TITLE
   ---          -----

    5.1  Opinion of Ropes & Gray*


   23.1  Consent of Deloitte & Touche LLP

   23.2  Consent of Ropes & Gray (included in the opinion filed as Exhibit 5.1)*

   24.1  Power of Attorney*

- ------------------
*  Previously filed.
    




                                      (16)
<PAGE>
ITEM 17.  UNDERTAKINGS

(A)  The undersigned registrant hereby undertakes:

          (1) to file,  during  any  period  in which  offers or sales are being
made, a post-effective amendment to this registration statement;

                  (i) to include any prospectus required by section 10(a)(3) of
          the Securities Act of  1933;

                  (ii) to reflect in the Prospectus any facts or events arising
          after the effective date of the registration statement (or the most
          recent post-effective amendment thereof) which, individually or in the
          aggregate, represent a fundamental change in the information set forth
          in the registration statement;

                  (iii) to include any material information with respect to the
          plan of distribution not previously disclosed in the registration
          statement or any material change to such information in the
          registration statement;

PROVIDED,  HOWEVER, that paragraphs (a)(1)(i) and (a)(1)(ii) do not apply if the
information  required  to be  included in a  post-effective  amendment  by those
paragraphs  is  contained  in periodic  reports  filed with or  furnished to the
Commission by the  registrant  pursuant to Section 13 or 15(d) of the Securities
Exchange Act of 1934 that are  incorporated  by  reference  in the  registration
statement.

          (2) that,  for the  purpose of  determining  any  liability  under the
Securities Act of 1933 (the "Act"), each such post-effective  amendment shall be
deemed to be a new registration statement of the securities offered therein, and
the offering of such  securities  at that time shall be deemed to be the initial
BONA FIDE offering thereof;

          (3) to remove from registration by means of a post-effective amendment
any of the securities being registered which remain unsold at the termination of
the offering;

          (4) insofar as indemnification  for liabilities  arising under the Act
may  be  permitted  to  directors,  officers,  and  controlling  persons  of the
registrant pursuant to the foregoing  provisions,  or otherwise,  the registrant
has been advised that in the opinion of the Securities  and Exchange  Commission
such  indemnification  is against  public policy as expressed in the Act and is,
therefore,  unenforceable. In the event that a claim for indemnification against
such liabilities  (other than the payment by the registrant of expenses incurred
or paid by a director,  officer,  or controlling person of the registrant in the
successful  defense of any  action,  suit or  proceeding)  is  asserted  by such
director,  officer or controlling person in connection with the securities being
registered, the registrant will, unless in the opinion of its counsel the matter
has been  settled by  controlling  precedent,  submit to a court of  appropriate
jurisdiction the question whether such  indemnification  by it is against public
policy as expressed in the Act and will be governed by the final adjudication of
such issue;

          (5) that,  for purposes of  determining  any liability  under the Act,
each filing of the registrant's annual report pursuant to Section 13(a) or 15(d)
of the Securities Exchange Act of 1934 (and, where applicable, each filing of an
employee  benefit  plan's  annual  report  pursuant  to  Section  15(d)  of  the
Securities  Exchange  Act of 1934)  that is  incorporated  by  reference  in the
registration  statement  shall  be  deemed  to be a new  registration  statement
relating to the securities offered therein,  and the offering of such securities
at that time shall be deemed to be the initial bona fide offering thereof; and

                                      (17)
<PAGE>

          (6) to deliver or cause to be delivered with the  Prospectus,  to each
person to whom the  Prospectus is sent or given,  the latest annual  report,  to
security  holders  that is  incorporated  by  reference  in the  Prospectus  and
furnished  pursuant to and meeting the requirements of Rule 14a-3 or 14c-3 under
the Securities  Exchange Act of 1934; and, where 
interim  financial  information
required to be presented by Article 3 of Regulation  S-X is not set forth in the
Prospectus,  to  deliver,  or cause to be  delivered  to each person to whom the
Prospectus is sent or given,  the latest  quarterly  report that is specifically
incorporated  by reference in the  Prospectus to provide such interim  financial
information.






                                      (18)
<PAGE>
                                   SIGNATURES

   
     Pursuant to the  requirements of the Securities Act of 1933, the Registrant
certifies  that it has  reasonable  grounds to believe  that it meets all of the
requirements  for filing on Form S-3 and has duly caused this Amendment No. 1 to
the  registration  statement  on Form  S-3 to be  signed  on its  behalf  by the
undersigned, thereunto duly authorized, in the Town of Lexington, Massachusetts,
on the 23rd day of October, 1997.
    
                                                        
                                        MACROCHEM CORPORATION


                                              /S/ Alvin J. Karloff
                                              --------------------
                                        By:   Alvin J. Karloff,
                                              Chief Executive Officer, 
                                              President and Director


   
     Pursuant to the  requirements of the Securities Act of 1933, this Amendment
No. 1 to the registration statement on Form S-3 has been signed by the following
persons in the capacities and on the dates indicated.


SIGNATURE                 CAPACITY                                   DATE
- ---------                 --------                                   ----

CARLOS M. SAMOUR*         Chairman of the Board and Director
- -----------------         
Carlos M. Samour          

/S/ ALVIN J. KARLOFF      Chief Executive                      October 23 , 1997
- --------------------                                                          
Alvin J. Karloff          Officer, President
                          and Director
                          (principal executive, financial, and 
                          accounting officer)

WILLARD M. BRIGHT*        Director
- ------------------        
Willard M. Bright

MICHAEL A. DAVIS*         Director
- -----------------         
Michael A. Davis

PETER G. MARTIN*          Director
- ----------------          
Peter G. Martin

STEPHEN J. RIGGI*         Vice President, Operations and Director
- -----------------         
Stephen J. Riggi          

/S/ALVIN J. KARLOFF
- --------------------
*  Alvin J. Karloff, Attorney-in-Fact
DATE:  October 23, 1997
    
                                     (19)
<PAGE>
                                  EXHIBIT INDEX

         DESCRIPTION
         -----------


   
         Consent of Deloitte & Touche LLP
    

                                      (20)
<PAGE>
                                     


                                                                   EXHIBIT 23.1
                                                                   ------------
INDEPENDENT AUDITORS' CONSENT

     We consent to the  incorporation  by reference in this  Amendment  No. 1 to
Registration  Statement  No.  333-34533 of MacroChem  Corporation  of our report
dated March 6, 1997,  appearing  in the Annual  Report on Form 10-K of MacroChem
Corporation  for the year ended  December  31, 1996 and to the  reference  to us
under  the  heading  "Experts"  in  the  Prospectus,   which  is  part  of  this
Registration Statement.

/S/ DELOITTE & TOUCHE LLP
DELOITTE & TOUCHE LLP
Boston, Massachusetts



October 22, 1997


                                      (21)
<PAGE>


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