<PAGE>

                                                    Registration No. 333-_____

    As filed with the Securities and Exchange Commission on November 22, 1999

------------------------------------------------------------------------------

                       SECURITIES AND EXCHANGE COMMISSION
                             Washington, D.C. 20549
                         -----------------------------

                                    FORM S-8
                          REGISTRATION STATEMENT UNDER
                           THE SECURITIES ACT OF 1933

                          ----------------------------

                                   HYSEQ, INC.
             (Exact name of registrant as specified in its charter)

          NEVADA                                              36-3855489
(State or other Jurisdiction                               (I.R.S. Employer
of incorporation or organization)                       Identification Number)

                 670 ALMANOR AVENUE, SUNNYVALE, CALIFORNIA 94086
              (Address of registrant's principal executive offices)

             HYSEQ, INC. NON-QUALIFIED EMPLOYEE STOCK PURCHASE PLAN
                            (Full title of the plan)

                               MR. LEWIS S. GRUBER
                      PRESIDENT AND CHIEF EXECUTIVE OFFICER
                                   HYSEQ, INC.
                               670 ALMANOR AVENUE
                           SUNNYVALE, CALIFORNIA 94086
                      (Name, address of agent for service)

                            TELEPHONE: (408) 524-8100
          (Telephone Number, including area code, of agent for service)

                         CALCULATION OF REGISTRATION FEE
<TABLE>
<CAPTION>
-------------------------- ---------------------- ---------------------- ---------------------- ----------------------
Title of each                  Amount to be         Proposed maximum       Proposed maximum           Amount of
class of securities            registered(2)       offering price per     aggregate offering     registration fee(3)
to be registered(1)                                     share(3)               price(3)
-------------------------- ---------------------- ---------------------- ---------------------- ----------------------
<S>                        <C>                    <C>                    <C>                    <C>
Common Stock, par value
$.001 per share                   50,000                  $5.30                $265,000                $73.67
-------------------------- ---------------------- ---------------------- ---------------------- ----------------------
</TABLE>

(1) In addition, pursuant to Rule 416(c) under the Securities Act of 1933, this
Registration Statement also covers an indeterminable amount of interests to be
offered or sold pursuant to the employee benefit described therein.

(2) This Registration Statement includes any additional shares of the
registrant's Common Stock that may be issued pursuant to antidilution provisions
contained in the plan.

(3) Pursuant to Rule 457 (c) and (h), the registration fee was computed on the
basis of the average of the high and low prices of the registrant's Common Stock
on the Nasdaq National Market on November 17, 1999.

<PAGE>

                                     PART I
                           INFORMATION REQUIRED IN THE
                            SECTION 10(a) PROSPECTUS

         ITEM 1.  PLAN INFORMATION

                  Not required to be included herewith.

         ITEM 2.  REGISTRANT INFORMATION AND EMPLOYEE PLAN ANNUAL INFORMATION

                  Not required to be included herewith.


                                     PART II

                           INFORMATION REQUIRED IN THE
                             REGISTRATION STATEMENT


         ITEM 3.  INCORPORATION OF DOCUMENTS BY REFERENCE.

         The following documents, which have heretofore been filed by Hyseq,
Inc. (the "Company") with the Securities and Exchange Commission (the
"Commission"), are incorporated by reference in this Registration Statement,
except to the extent that any statement or information therein is modified,
superseded or replaced by a statement or information contained in any other
subsequently filed document incorporated herein by reference:

         i.       the Company's Annual Report on Form 10-K for the year ended
                  December 31, 1998;

         ii.      the Company's Quarterly Report on Form 10-Q for the quarters
                  ended March 31, 1999, June 30, 1999 and November 12, 1999;

         iii.     the Company's Proxy Statement on Form 14A, filed on May 14,
                  1999; and

         iv.      the description of the Company's Common Stock contained in the
                  Company's Registration Statement on Form 8-A, dated July 23,
                  1997.

All documents filed by the Company or the plans pursuant to Sections 13(a),
13(c), 14 and 15(d) of the Exchange Act after the date hereof, and prior to the
filing of a post - effective amendment which indicates that all securities
offered have been sold or which deregisters all securities then remaining
unsold, shall be deemed to be incorporated by reference herein and to be a part
hereof from the date of filing of such documents.

                                       2

<PAGE>

         ITEM 4.  DESCRIPTION OF SECURITIES.

         Not applicable.

         ITEM 5.  INTERESTS OF NAMED EXPERTS AND COUNSEL.

         Not applicable.

         ITEM 6.  INDEMNIFICATION OF DIRECTORS AND OFFICERS.

         As permitted by the Nevada General Corporation Law, the Company's
Articles and By-Laws provide that officers and directors of the Company shall
not be personally liable for monetary damages to the Company for certain
breaches of their fiduciary duty as directors, unless they violated their duty
of loyalty to the Company or its stockholders, acted in bad faith, knowingly or
intentionally violated the law, authorized illegal dividends or redemptions, or
derived an improper personal benefit from their action as directors. This
provision would have no effect on the availability of equitable remedies or
nonmonetary relief, such as an injunction or rescission for breach of the duty
of care. Directors will, however, no longer be liable for monetary damages
arising from decisions involving violations of the duty of care which could be
deemed grossly negligent.

         The By-Laws provide that directors of the Company shall be indemnified
by the Company to the fullest extent authorized by Nevada law, as it now exists
or may in the future be amended, against all expenses and liabilities reasonably
incurred in connection with service for or on behalf of the Company. The By-Laws
also authorize the Company to enter into one or more agreements with any person
which provide for indemnification greater or different from that provided in the
Articles. The Company has entered into indemnification agreements with all
current officers and members of the Board of Directors. Insofar as
indemnification for liabilities arising under the Securities Act may be
permitted to directors, officers and controlling persons of the Company pursuant
to the foregoing provisions, or otherwise, the Company has been advised that in
the opinion of the Commission such indemnification is against public policy as
expressed in the Securities Act and is, therefore, unenforceable.

         ITEM 7.  EXEMPTION FROM REGISTRATION CLAIMED.

         Not applicable.

         ITEM 8.  EXHIBITS.

         See Exhibit Index which is incorporated herein by reference.

         ITEM 9.  UNDERTAKINGS.

         (a)      The undersigned registrant hereby undertakes:

                                       3

<PAGE>

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

                  i.    include any prospectus required by Section 10(a)(3)
                        of the Securities Act of 1933 (the "Securities Act");

                  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 registration statement is on Form S-3 or Form
                  S-8, and the information required to be included in a
                  post-effective amendment by those paragraphs is contained in
                  periodic reports filed by the registrant pursuant to Section
                  13 or Section 15(d) of the Exchange Act that are incorporated
                  by reference in the registration statement.

        (2)       That, for the purpose of determining any liability under the
                  Securities Act, each such post-effective amendment 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.

        (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.

  (b)   The undersigned registrant hereby undertakes that, for
        purposes of determining any liability under the Securities Act
        of 1933, each filing of the registrant's annual report
        pursuant to Section 13(a) or Section 15(d) of the Exchange Act
        and each filing of the plan's annual report pursuant to
        Section 15(d) of the Exchange Act 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.

 (c)    Insofar as indemnification for liabilities arising under the Securities
        Act may be permitted to officers, directors, and controlling persons of
        the registrant pursuant to

                                       4

<PAGE>

        the registrant's certificate of incorporation or by-laws, or
        otherwise, the registrant has been advised that in the opinion of the
        Commission such indemnification is against public policy as expressed
        in the Securities 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 Securities Act and will be governed by the final
        adjudication of such issue.

                                   SIGNATURES

         THE REGISTRANT. 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-8 and has duly caused this
registration statement to be signed on its behalf by the undersigned, thereunto
duly authorized, in the City of Sunnyvale, State of California, on the 18th day
of November, 1999.

                                   Hyseq, Inc.


                                   By: /s/ Lewis S. Gruber
                                       -------------------------------------
                                       Lewis S. Gruber
                                       President and Chief Executive Officer






                                       5

<PAGE>

                                POWER OF ATTORNEY

         Know all men by these presents, that each person whose signature
appears below constitutes and appoints Lewis S. Gruber and Mark E. Gitter, and
each of them singly, his true and lawful attorneys-in-fact and agents, with full
power of substitution and resubstitution, for him and in his name, place and
stead, in any and all capacities (including his capacity as a director and/or
officer of Hyseq, Inc.) to sign any and all amendments (including post-effective
amendments) to this Registration Statement, and to file the same, with all
exhibits thereto, and other documents in connection therewith, with the
Securities and Exchange Commission, granting unto said attorneys-in-fact and
agents, and each of them, full power and authority to do and perform each and
every act and thing requisite and necessary to be done in and about the
premises, as fully to all intents and purposes as he might or could do in
person, hereby ratifying and confirming all that said attorneys-in-fact and
agents or any of them, or their or his substitute or substitutes, may lawfully
do or cause to be done by virtue thereof.

         IN WITNESS WHEREOF, the undersigned have executed this power of
attorney on the 18th day of November, 1999.


/s/ Robert D. Weist                              /s/ Lewis S. Gruber
---------------------------------                -----------------------------
Robert D. Weist                                      Lewis S. Gruber


/s/ Mark E. Gitter                               /s/ Greta E. Marshall
---------------------------------                -----------------------------
Mark E. Gitter                                       Greta E. Marshall


/s/ Radoje T. Drmanac                            /s/ Ernst Schweizer
---------------------------------                -----------------------------
Radoje T. Drmanac.                                   Ernst Schweizer


/s/ Raymond F. Baddour                           /s/ Thomas N. McCarter
---------------------------------                -----------------------------
Raymond F. Baddour                                   Thomas N. McCarter III





                                       6

<PAGE>

         Pursuant to the requirements of the Securities Act of 1933, this
registration statement has been signed by the following persons in their
respective capacities on the 18th day of November, 1999.

<TABLE>
<CAPTION>
     Signature                                         Title
     ---------                                         -----
<S>                                         <C>
/s/ Robert D. Weist
----------------------------------
Robert D. Weist                             Chairman of the Board


/s/ Lewis S. Gruber
----------------------------------
Lewis S. Gruber                             President and Chief Executive Officer, Director
                                            (Principal Executive Officer)

/s/ Mark E. Gitter
----------------------------------
Mark E. Gitter                              Chief Financial Officer
                                            (Principal Financial and Accounting Officer)

/s/ Radoje T. Drmanac
----------------------------------
Radoje T. Drmanac                           Director


/s/ Raymond F. Baddour
----------------------------------
Raymond F. Baddour                          Director


/s/ Greta E. Marshall
----------------------------------
Greta E. Marshall                           Director


/s/ Thomas N. NcCarter III
----------------------------------
Thomas N. McCarter III                      Director


/s/ Ernst Schweizer
----------------------------------
Ernst Schweizer                             Director
</TABLE>








                                       7

<PAGE>

THE PLAN. Pursuant to the requirements of the Securities Act of 1933, the Hyseq,
Inc. Non-Qualified Employee Stock Purchase Plan has duly caused this
Registration Statement to be signed on its behalf by the undersigned, thereunto
duly authorized, in the City of Sunnyvale, State of California, on the 18th day
of November, 1999.


                                                Hyseq, Inc.


                                                By: /s/ Lewis S. Gruber
                                                    -------------------
                                                On Behalf of the Committee








                                       8

<PAGE>

                                  EXHIBIT INDEX

<TABLE>
<CAPTION>
Exhibit
 Number                          Description of Exhibit
-------                          ----------------------
<S>               <C>
  4.1             Specimen Stock Certificate *

  4.2             Certificate of Incorporation of Hyseq, Inc. as amended to date*

  4.3             By-Laws of Hyseq, Inc., *

  4.4             First Amendment to the By-Laws of Hyseq, Inc. **

  5               Opinion of Sachnoff & Weaver, Ltd.

 23               Consent of Ernst & Young LLP, Independent Auditors

 24               Powers of Attorney (included as part of the signature page of this
                  Registration Statement)
</TABLE>
------------------------------


*   Filed as an exhibit to the Company's Registration Statement on Form S-1,
    Registration Statement No. 333-29091, declared effective by the Securities
    and Exchange Commission on August 7, 1997, and incorporated herein by
    reference.

**  Filed as an exhibit to the Company's Annual Report on Form 10-K for the year
    ended December 31, 1998, and incorporated herein by reference.
[{"type": "S-8", "sequence": "1", "description": "S-8", "secsgml_size_bytes": 18532}]
{"company-data": {"conformed-name": "HYSEQ INC", "cik": "0000907654", "assigned-sic": "2835", "irs-number": "363855489", "state-of-incorporation": "NV", "fiscal-year-end": "1231"}, "filing-values": {"form-type": "S-8", "act": "33", "file-number": "333-91471", "film-number": "99762466"}, "business-address": {"street1": "670 ALMANOR AVE", "city": "SUNNYVALE", "state": "CA", "zip": "94086", "phone": "4085248100"}, "mail-address": {"street1": "670 ALMANOR AVE", "city": "SUNNYVALE", "state": "CA", "zip": "94086"}}
Registration No. 333-_____

    As filed with the Securities and Exchange Commission on November 22, 1999

------------------------------------------------------------------------------

                       SECURITIES AND EXCHANGE COMMISSION
                             Washington, D.C. 20549
                         -----------------------------

                                    FORM S-8
                          REGISTRATION STATEMENT UNDER
                           THE SECURITIES ACT OF 1933

                          ----------------------------

                                   HYSEQ, INC.
             (Exact name of registrant as specified in its charter)

          NEVADA                                              36-3855489
(State or other Jurisdiction                               (I.R.S. Employer
of incorporation or organization)                       Identification Number)

                 670 ALMANOR AVENUE, SUNNYVALE, CALIFORNIA 94086
              (Address of registrant's principal executive offices)

             HYSEQ, INC. NON-QUALIFIED EMPLOYEE STOCK PURCHASE PLAN
                            (Full title of the plan)

                               MR. LEWIS S. GRUBER
                      PRESIDENT AND CHIEF EXECUTIVE OFFICER
                                   HYSEQ, INC.
                               670 ALMANOR AVENUE
                           SUNNYVALE, CALIFORNIA 94086
                      (Name, address of agent for service)

                            TELEPHONE: (408) 524-8100
          (Telephone Number, including area code, of agent for service)

                         CALCULATION OF REGISTRATION FEE
-------------------------- ---------------------- ---------------------- ---------------------- ----------------------
Title of each                  Amount to be         Proposed maximum       Proposed maximum           Amount of
class of securities            registered(2)       offering price per     aggregate offering     registration fee(3)
to be registered(1)                                     share(3)               price(3)
-------------------------- ---------------------- ---------------------- ---------------------- ----------------------
Common Stock, par value
$.001 per share                   50,000                  $5.30                $265,000                $73.67
-------------------------- ---------------------- ---------------------- ---------------------- ----------------------
(1) In addition, pursuant to Rule 416(c) under the Securities Act of 1933, this
Registration Statement also covers an indeterminable amount of interests to be
offered or sold pursuant to the employee benefit described therein.

(2) This Registration Statement includes any additional shares of the
registrant's Common Stock that may be issued pursuant to antidilution provisions
contained in the plan.

(3) Pursuant to Rule 457 (c) and (h), the registration fee was computed on the
basis of the average of the high and low prices of the registrant's Common Stock
on the Nasdaq National Market on November 17, 1999.
PART I
                           INFORMATION REQUIRED IN THE
                            SECTION 10(a) PROSPECTUS

         ITEM 1.  PLAN INFORMATION

                  Not required to be included herewith.

         ITEM 2.  REGISTRANT INFORMATION AND EMPLOYEE PLAN ANNUAL INFORMATION

                  Not required to be included herewith.

                                     PART II

                           INFORMATION REQUIRED IN THE
                             REGISTRATION STATEMENT

         ITEM 3.  INCORPORATION OF DOCUMENTS BY REFERENCE.

         The following documents, which have heretofore been filed by Hyseq,
Inc. (the "Company") with the Securities and Exchange Commission (the
"Commission"), are incorporated by reference in this Registration Statement,
except to the extent that any statement or information therein is modified,
superseded or replaced by a statement or information contained in any other
subsequently filed document incorporated herein by reference:

         i.       the Company's Annual Report on Form 10-K for the year ended
                  December 31, 1998;

         ii.      the Company's Quarterly Report on Form 10-Q for the quarters
                  ended March 31, 1999, June 30, 1999 and November 12, 1999;

         iii.     the Company's Proxy Statement on Form 14A, filed on May 14,
                  1999; and

         iv.      the description of the Company's Common Stock contained in the
                  Company's Registration Statement on Form 8-A, dated July 23,
                  1997.

All documents filed by the Company or the plans pursuant to Sections 13(a),
13(c), 14 and 15(d) of the Exchange Act after the date hereof, and prior to the
filing of a post - effective amendment which indicates that all securities
offered have been sold or which deregisters all securities then remaining
unsold, shall be deemed to be incorporated by reference herein and to be a part
hereof from the date of filing of such documents.

                                       2
ITEM 4.  DESCRIPTION OF SECURITIES.

         Not applicable.

         ITEM 5.  INTERESTS OF NAMED EXPERTS AND COUNSEL.

         Not applicable.

         ITEM 6.  INDEMNIFICATION OF DIRECTORS AND OFFICERS.

         As permitted by the Nevada General Corporation Law, the Company's
Articles and By-Laws provide that officers and directors of the Company shall
not be personally liable for monetary damages to the Company for certain
breaches of their fiduciary duty as directors, unless they violated their duty
of loyalty to the Company or its stockholders, acted in bad faith, knowingly or
intentionally violated the law, authorized illegal dividends or redemptions, or
derived an improper personal benefit from their action as directors. This
provision would have no effect on the availability of equitable remedies or
nonmonetary relief, such as an injunction or rescission for breach of the duty
of care. Directors will, however, no longer be liable for monetary damages
arising from decisions involving violations of the duty of care which could be
deemed grossly negligent.

         The By-Laws provide that directors of the Company shall be indemnified
by the Company to the fullest extent authorized by Nevada law, as it now exists
or may in the future be amended, against all expenses and liabilities reasonably
incurred in connection with service for or on behalf of the Company. The By-Laws
also authorize the Company to enter into one or more agreements with any person
which provide for indemnification greater or different from that provided in the
Articles. The Company has entered into indemnification agreements with all
current officers and members of the Board of Directors. Insofar as
indemnification for liabilities arising under the Securities Act may be
permitted to directors, officers and controlling persons of the Company pursuant
to the foregoing provisions, or otherwise, the Company has been advised that in
the opinion of the Commission such indemnification is against public policy as
expressed in the Securities Act and is, therefore, unenforceable.

         ITEM 7.  EXEMPTION FROM REGISTRATION CLAIMED.

         Not applicable.

         ITEM 8.  EXHIBITS.

         See Exhibit Index which is incorporated herein by reference.

         ITEM 9.  UNDERTAKINGS.

         (a)      The undersigned registrant hereby undertakes:

                                       3
(1)      To file, during any period in which offers or sales are being
                  made, a post-effective amendment to this registration
                  statement:

                  i.    include any prospectus required by Section 10(a)(3)
                        of the Securities Act of 1933 (the "Securities Act");

                  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 registration statement is on Form S-3 or Form
                  S-8, and the information required to be included in a
                  post-effective amendment by those paragraphs is contained in
                  periodic reports filed by the registrant pursuant to Section
                  13 or Section 15(d) of the Exchange Act that are incorporated
                  by reference in the registration statement.

        (2)       That, for the purpose of determining any liability under the
                  Securities Act, each such post-effective amendment 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.

        (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.

  (b)   The undersigned registrant hereby undertakes that, for
        purposes of determining any liability under the Securities Act
        of 1933, each filing of the registrant's annual report
        pursuant to Section 13(a) or Section 15(d) of the Exchange Act
        and each filing of the plan's annual report pursuant to
        Section 15(d) of the Exchange Act 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.

 (c)    Insofar as indemnification for liabilities arising under the Securities
        Act may be permitted to officers, directors, and controlling persons of
        the registrant pursuant to

                                       4
the registrant's certificate of incorporation or by-laws, or
        otherwise, the registrant has been advised that in the opinion of the
        Commission such indemnification is against public policy as expressed
        in the Securities 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 Securities Act and will be governed by the final
        adjudication of such issue.

                                   SIGNATURES

         THE REGISTRANT. 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-8 and has duly caused this
registration statement to be signed on its behalf by the undersigned, thereunto
duly authorized, in the City of Sunnyvale, State of California, on the 18th day
of November, 1999.

                                   Hyseq, Inc.

                                   By: /s/ Lewis S. Gruber
                                       -------------------------------------
                                       Lewis S. Gruber
                                       President and Chief Executive Officer

                                       5
POWER OF ATTORNEY

         Know all men by these presents, that each person whose signature
appears below constitutes and appoints Lewis S. Gruber and Mark E. Gitter, and
each of them singly, his true and lawful attorneys-in-fact and agents, with full
power of substitution and resubstitution, for him and in his name, place and
stead, in any and all capacities (including his capacity as a director and/or
officer of Hyseq, Inc.) to sign any and all amendments (including post-effective
amendments) to this Registration Statement, and to file the same, with all
exhibits thereto, and other documents in connection therewith, with the
Securities and Exchange Commission, granting unto said attorneys-in-fact and
agents, and each of them, full power and authority to do and perform each and
every act and thing requisite and necessary to be done in and about the
premises, as fully to all intents and purposes as he might or could do in
person, hereby ratifying and confirming all that said attorneys-in-fact and
agents or any of them, or their or his substitute or substitutes, may lawfully
do or cause to be done by virtue thereof.

         IN WITNESS WHEREOF, the undersigned have executed this power of
attorney on the 18th day of November, 1999.

/s/ Robert D. Weist                              /s/ Lewis S. Gruber
---------------------------------                -----------------------------
Robert D. Weist                                      Lewis S. Gruber

/s/ Mark E. Gitter                               /s/ Greta E. Marshall
---------------------------------                -----------------------------
Mark E. Gitter                                       Greta E. Marshall

/s/ Radoje T. Drmanac                            /s/ Ernst Schweizer
---------------------------------                -----------------------------
Radoje T. Drmanac.                                   Ernst Schweizer

/s/ Raymond F. Baddour                           /s/ Thomas N. McCarter
---------------------------------                -----------------------------
Raymond F. Baddour                                   Thomas N. McCarter III

                                       6
Pursuant to the requirements of the Securities Act of 1933, this
registration statement has been signed by the following persons in their
respective capacities on the 18th day of November, 1999.
Signature                                         Title
     ---------                                         -----
/s/ Robert D. Weist
----------------------------------
Robert D. Weist                             Chairman of the Board

/s/ Lewis S. Gruber
----------------------------------
Lewis S. Gruber                             President and Chief Executive Officer, Director
                                            (Principal Executive Officer)

/s/ Mark E. Gitter
----------------------------------
Mark E. Gitter                              Chief Financial Officer
                                            (Principal Financial and Accounting Officer)

/s/ Radoje T. Drmanac
----------------------------------
Radoje T. Drmanac                           Director

/s/ Raymond F. Baddour
----------------------------------
Raymond F. Baddour                          Director

/s/ Greta E. Marshall
----------------------------------
Greta E. Marshall                           Director

/s/ Thomas N. NcCarter III
----------------------------------
Thomas N. McCarter III                      Director

/s/ Ernst Schweizer
----------------------------------
Ernst Schweizer                             Director
7
THE PLAN. Pursuant to the requirements of the Securities Act of 1933, the Hyseq,
Inc. Non-Qualified Employee Stock Purchase Plan has duly caused this
Registration Statement to be signed on its behalf by the undersigned, thereunto
duly authorized, in the City of Sunnyvale, State of California, on the 18th day
of November, 1999.

                                                Hyseq, Inc.

                                                By: /s/ Lewis S. Gruber
                                                    -------------------
                                                On Behalf of the Committee

                                       8
EXHIBIT INDEX
Exhibit
 Number                          Description of Exhibit
-------                          ----------------------
4.1             Specimen Stock Certificate *

  4.2             Certificate of Incorporation of Hyseq, Inc. as amended to date*

  4.3             By-Laws of Hyseq, Inc., *

  4.4             First Amendment to the By-Laws of Hyseq, Inc. **

  5               Opinion of Sachnoff & Weaver, Ltd.

 23               Consent of Ernst & Young LLP, Independent Auditors

 24               Powers of Attorney (included as part of the signature page of this
                  Registration Statement)
------------------------------

*   Filed as an exhibit to the Company's Registration Statement on Form S-1,
    Registration Statement No. 333-29091, declared effective by the Securities
    and Exchange Commission on August 7, 1997, and incorporated herein by
    reference.

**  Filed as an exhibit to the Company's Annual Report on Form 10-K for the year
    ended December 31, 1998, and incorporated herein by reference.