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                                                                     EXHIBIT 4.5

                                 Amendment No. 1
                                       to
                    Hyseq, Inc. Employee Stock Purchase Plan

     WHEREAS, the Board of Directors and the Stockholders of Hyseq, Inc. have
approved the following amendment to Section 5 of the Hyseq, Inc. Employee Stock
Purchase Plan (the "Stock Purchase Plan") to be effective as of May 23, 2000.

     NOW, THEREFORE, Section 5 of the Stock Purchase Plan is hereby amended to
increase the maximum number of shares of Common Stock which may be issued for
all purposes under the Stock Purchase Plan from 50,000 to 250,000.

     All other provisions of the Stock Purchase Plan remain in full force and
effect.



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