<PAGE>

      As filed with the Securities and Exchange Commission on May 1, 2001

                                                      Registration No. 333-_____

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

                       SECURITIES AND EXCHANGE COMMISSION
                             WASHINGTON, D.C. 20549

                                    FORM S-8

                          REGISTRATION STATEMENT UNDER
                           THE SECURITIES ACT OF 1933

                          TRANSKARYOTIC THERAPIES, INC.

             (Exact Name of Registrant as Specified in Its Charter)

<TABLE>
<S>                                                                        <C>

         DELAWARE                                                            04-3027191
(State or Other Jurisdiction of                                           (I.R.S. Employer
Incorporation or Organization)                                            Identification No.)

         195 ALBANY STREET                                                      02139
     CAMBRIDGE, MASSACHUSETTS
(Address of Principal Executive Offices)                                      (Zip Code)
</TABLE>

               2001 NON-OFFICER, NON-DIRECTOR STOCK INCENTIVE PLAN
                            (Full Title of the Plan)

                                RICHARD F SELDEN
                      PRESIDENT AND CHIEF EXECUTIVE OFFICER
                                195 ALBANY STREET
                            CAMBRIDGE, MASSACHUSETTS
                     (Name and Address of Agent For Service)
                                  617-340-0200
          (Telephone Number, Including Area Code, of Agent For Service)


                         CALCULATION OF REGISTRATION FEE

<TABLE>
<CAPTION>

====================================================================================================================
Title of Securities to be                            Proposed Maximum       Proposed Maximum
Registered                       Amount to be       Offering Price Per     Aggregate Offering        Amount of
                                  Registered               Share                 Price           Registration Fee
--------------------------------------------------------------------------------------------------------------------
<S>                           <C>                  <C>                    <C>                   <C>

Common Stock, $0.01 par
value per share (including    2,000,000 shares     $15.835(1)             $31,670,000(1)        $7,918
the associated Preferred
Stock Purchase Rights)
====================================================================================================================
</TABLE>

(1)      Estimated solely for the purpose of calculating the registration fee
         pursuant to Rules 457(c) and 457(h) of the Securities Act of 1933, as
         amended, and based upon the average of the high and low prices of the
         Registrant's Common Stock as reported on the Nasdaq National Market on
         April 25, 2001.

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

<PAGE>


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

         ITEM 1. PLAN INFORMATION.

         The information required by Item 1 is included in documents sent or
given to participants in the plan covered by this registration statement
pursuant to Rule 428(b)(1) of the Securities Act of 1933, as amended (the
"Securities Act").

         ITEM 2. REGISTRANT INFORMATION AND EMPLOYEE PLAN ANNUAL INFORMATION.

         The written statement required by Item 2 is included in documents sent
or given to participants in the plans covered by this registration statement
pursuant to Rule 428(b)(1) of the Securities Act.


                                     PART II
               INFORMATION REQUIRED IN THE REGISTRATION STATEMENT

         ITEM 3. INCORPORATION OF DOCUMENTS BY REFERENCE.

         The registrant is subject to the informational and reporting
requirements of Sections 13(a), 14, and 15(d) of the Securities Exchange Act of
1934, as amended (the "Exchange Act"), and in accordance therewith files
reports, proxy statements and other information with the Securities and Exchange
Commission (the "Commission"). The following documents, which are on file with
the Commission, are incorporated in this registration statement by reference:

         (a) The registrant's latest annual report filed pursuant to Section
13(a) or 15(d) of the Exchange Act or the latest prospectus filed pursuant to
Rule 424(b) under the Securities Act that contains audited financial statements
for the registrant's latest fiscal year for which such statements have been
filed.

         (b) All other reports filed pursuant to Section 13(a) or 15(d) of the
Exchange Act since the end of the fiscal year covered by the document referred
to in (a) above.

         (c) The description of the securities contained in the registrant's
registration statement on Form 8-A and filed under the Exchange Act, including
any amendment or report filed for the purpose of updating such description.

         All documents subsequently filed by the registrant pursuant to Sections
13(a), 13(c), 14 and 15(d) of the Exchange Act, prior to the filing of a
post-effective amendment which indicates that all securities offered hereby have
been sold or which deregisters all securities then remaining unsold, shall be
deemed to be incorporated by reference in this registration statement and to be
part hereof from the date of the filing of such documents. Any statement
contained in a document incorporated or deemed to be incorporated by reference
herein shall be deemed to be modified or superseded for the purposes of this
registration statement to the extent that a statement contained herein or in any
other subsequently filed document which also is or is deemed to be incorporated
by reference herein modifies or supersedes such statement. Any statement so
modified or superseded shall not be deemed, except as so modified or superseded,
to constitute a part of this registration statement.


                                      -1-
<PAGE>

         ITEM 4. DESCRIPTION OF SECURITIES.

         Not applicable.

         ITEM 5. INTERESTS OF NAMED EXPERTS AND COUNSEL.

         Hale and Dorr LLP has opined as to the legality of the securities being
offered by this registration statement.

         ITEM 6. INDEMNIFICATION OF DIRECTORS AND OFFICERS.

         Article VII of the registrant's Amended and Restated Certificate of
Incorporation provides that no director of the registrant shall be personally
liable for any monetary damages for any breach of fiduciary duty as a director,
except to the extent that the Delaware General Corporation Law prohibits the
elimination or limitation of liability of directors for breach of fiduciary
duty.

         Article VIII of the registrant's Amended and Restated Certificate of
Incorporation provides that a director or officer of the registrant (a) shall be
indemnified by the registrant against all expenses (including attorneys' fees),
judgments, fines and amounts paid in settlement incurred in connection with any
litigation or other legal proceeding (other than an action by or in the right of
the registrant) brought against him by virtue of his position as a director or
officer of the registrant if he acted in good faith and in a manner he
reasonably believed to be in, or not opposed to, the best interests of the
registrant, and, with respect to any criminal action or proceeding, had no
reasonable cause to believe his conduct was unlawful and (b) shall be
indemnified by the registrant against all expenses (including attorneys' fees)
and amounts paid in settlement incurred in connection with any action by or in
the right of the registrant brought against him by virtue of his position as a
director or officer of the registrant if he acted in good faith and in a manner
he reasonably believed to be in, or not opposed to, the best interests of the
registrant, except that no indemnification shall be made with respect to any
matter as to which such person shall have been adjudged to be liable to the
registrant, unless a court determines that, despite such adjudication but in
view of all of the circumstances, he is entitled to indemnification of such
expenses. Notwithstanding the foregoing, to the extent that a director or
officer has been successful, on the merits or otherwise, including, without
limitation, the dismissal of an action without prejudice, he is required to be
indemnified by the registrant against all expenses (including attorneys' fees)
incurred in connection therewith. Expenses shall be advanced to a director or
officer at his request, provided that he undertakes to repay the amount advanced
if it is ultimately determined that he is not entitled to indemnification for
such expenses.

         Indemnification is required to be made unless the registrant determines
that the applicable standard of conduct required for indemnification has not
been met. In the event of a determination by the registrant that the director or
officer did not meet the applicable standard of conduct required for
indemnification, or if the registrant fails to make an indemnification payment
within 60 days after such payment is claimed by such person, such person is
permitted to petition the court to make an independent determination as to
whether such person is entitled to indemnification. As a condition precedent to
the right of indemnification, the director or officer must give notice of the
action for which indemnity is sought and the registrant has the right to
participate in such action or assume the defense thereof.

         Article VIII of the registrant's Amended and Restated Certificate of
Incorporation further provides that the indemnification provided therein is not
exclusive, and provides that in the event


                                      -2-
<PAGE>

that the Delaware General Corporation Law is amended to expand the
indemnification permitted to directors or officers the registrant must indemnify
those persons to the fullest extent permitted by such law as so amended.

         Article VIII, Section 8 of the registrant's By-Laws provides that the
registrant shall indemnify any and all of the registrant's directors or officers
to the fullest extent permitted by the Delaware General Corporation Law.

         Section 145 of the Delaware General Corporation Law provides that a
corporation has the power to indemnify a director, officer, employee or agent of
the corporation and certain other persons serving at the request of the
corporation in related capacities against amounts paid and expenses incurred in
connection with an action or proceeding to which he is or is threatened to be
made a party by reason of such position, if such person shall have 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 any criminal proceeding, if such person
had no reasonable cause to believe his conduct was unlawful; provided that, in
the case of actions brought by or in the right of the corporation, no
indemnification shall be made with respect to any matter as to which such person
shall have been adjudged to be liable to the corporation unless and only to the
extent that the adjudicating court determines that such indemnification is
proper under the circumstances.

         The registrant maintains a general liability insurance policy which
covers certain liabilities of directors and officers of the registrant arising
out of claims based on acts or omissions in their capacities as directors or
officers.

         ITEM 7. EXEMPTION FROM REGISTRATION CLAIMED.

         Not applicable.

         ITEM 8. EXHIBITS.

         The Exhibit Index immediately preceding the exhibits is incorporated
herein by reference.

         ITEM 9. UNDERTAKINGS.

         1. ITEM 512(a) OF REGULATION S-K. 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;

                      (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. Notwithstanding the foregoing, any
         increase or decrease in volume of securities offered (if the total
         dollar value of securities offered would not exceed that which was
         registered) and any deviation from the low or high end of the estimated
         maximum offering range may be reflected in the form of prospectus filed
         with the Commission pursuant to Rule 424(b) if, in the aggregate, the


                                       -3-
<PAGE>

         changes in volume and price represent no more than 20 percent change in
         the maximum aggregate offering price set forth in "Calculation of
         Registration Fee" table in the effective registration statement; and

                       (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 (i) and (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
         Section 15(d) of the Exchange Act that are incorporated by reference in
         this 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.

         2. ITEM 512(b) OF REGULATION S-K. The undersigned registrant hereby
undertakes that, for purposes of determining any liability under the Securities
Act, each filing of the registrant's annual report pursuant to Section 13(a) or
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.

         3. ITEM 512(h) OF REGULATION S-K. Insofar as indemnification for
liabilities arising under the Securities 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 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.


                                      -4-
<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-8 and has duly caused this registration
statement to be signed on its behalf by the undersigned, thereunto duly
authorized, in Cambridge, Massachusetts, on this 1st day of May, 2001.


                                    TRANSKARYOTIC THERAPIES, INC.


                                    By:  /s/ Richard F Selden
                                         --------------------------------------
                                         Richard F Selden
                                         President and Chief Executive Officer


                        POWER OF ATTORNEY AND SIGNATURES

         We, the undersigned officers and directors of Transkaryotic Therapies,
hereby severally constitute and appoint Richard F Selden, Daniel E. Geffken and
Michael J. Astrue and each of them singly, our true and lawful attorneys with
full power to them, and each of them singly, to sign for us and in our names in
the capacities indicated below, the registration statement on Form S-8 filed
herewith and any and all subsequent amendments to said registration statement,
and generally to do all such things in our names and on our behalf in our
capacities as officers and directors to enable Transkaryotic Therapies, Inc. to
comply with the provisions of the Securities Act of 1933, as amended, and all
requirements of the Securities and Exchange Commission, hereby ratifying and
confirming our signatures as they may be signed by our said attorneys, or any of
them, to said registration statement and any and all amendments thereto.

         Pursuant to the requirements of the Securities Act of 1933, this
registration statement has been signed by the following persons in the
capacities and on the dates indicated.

<TABLE>
<CAPTION>

             SIGNATURE                              TITLE                                DATE

<S>                                  <C>                                          <C>

/s/ Richard F Selden                  President, Chief Executive                    May 1, 2001
---------------------------           Officer and Director (Principal
Richard F Selden                      executive officer)



/s/ Daniel E. Geffken                 Senior Vice President, Finance                May 1, 2001
---------------------------           and Chief Financial Officer
Daniel E. Geffken                     (Principal financial and
                                      accounting officer)



/s/ Rodman W. Moorhead, III           Director                                      May 1, 2001
---------------------------
Rodman W. Moorhead, III



/s/ Jonathan S. Leff                  Director                                      May 1, 2001
---------------------------
Jonathan S. Leff


                                      -5-
<PAGE>


/s/ William R. Miller                 Director                                      May 1, 2001
---------------------------
William R. Miller



/s/ Walter Gilbert                    Director                                      May 1, 2001
---------------------------
Walter Gilbert



/s/ James E. Thomas                   Director                                      May 1, 2001
---------------------------
James E. Thomas



/s/ Wayne P. Yetter                   Director                                      May 1, 2001
---------------------------
Wayne P. Yetter
</TABLE>


                                      -6-
<PAGE>


                                INDEX TO EXHIBITS
<TABLE>
<CAPTION>

NUMBER                       DESCRIPTION
------                       -----------
<S>                         <C>

4.1(1)                       Amended and Restated Certificate of Incorporation of the Registrant

4.2(2)                       Certificate of Amendment of Amended and Restated Certificate of the Registrant

4.3(2)                       Certificate of Designation, Number, Voting Powers, Preferences and Rights of
                             Series A Convertible Preferred Stock of the Registrant

4.4(3)                       Certificate of Designations of Series B Junior Participating Preferred Stock
                             of the Registrant

4.5(3)                       Second Amended and Restated By-Laws of the Registrant

4.6(4)                       Rights Agreement dated December 13, 2000 between the Registrant and EquiServe
                             Trust Company, N.A., as rights agent

5.1                          Opinion of Hale and Dorr LLP, counsel to the Registrant

23.1                         Consent of Hale and Dorr LLP (included in Exhibit 5.1)

23.2                         Consent of Ernst & Young, LLP

24.1                         Power of attorney (included on the signature pages of this registration
                             statement)
</TABLE>

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

(1)      Previously filed with the Securities and Exchange Commission as an
         Exhibit to the Registrant's Quarterly Report on Form 10-Q for the
         quarter ended September 30, 1996 (File No. 0-21481) and incorporated
         herein by reference.

(2)      Previously filed with the Securities and Exchange Commission as an
         Exhibit to the Registrant's Quarterly Report on Form 10-Q for the
         quarter ended June 30, 2000 (File No. 0-21481) and incorporated herein
         by reference.

(3)      Previously filed with the Securities and Exchange Commission as an
         Exhibit to the Registrant's Annual Report on Form 10-K for the year
         ended December 31, 2000 (File No. 0-21481) and incorporated herein by
         reference.

(4)      Previously filed with the Securities and Exchange Commission as an
         Exhibit to the Registrant's Current Report on Form 8-K dated as of
         December 14, 2000 and incorporated herein by reference.
[{"type": "S-8", "sequence": "1", "filename": "a2046509zs-8.txt", "description": "FORM S-8", "secsgml_size_bytes": 22592}]
{"company-data": {"conformed-name": "TRANSKARYOTIC THERAPIES INC", "cik": "0000885259", "assigned-sic": "2836", "irs-number": "043027191", "state-of-incorporation": "DE", "fiscal-year-end": "1231"}, "filing-values": {"form-type": "S-8", "act": "33", "file-number": "333-59910", "film-number": "1618408"}, "business-address": {"street1": "195 ALBANY ST", "city": "CAMBRIDGE", "state": "MA", "zip": "02139", "phone": "6173490200"}}
As filed with the Securities and Exchange Commission on May 1, 2001

                                                      Registration No. 333-_____

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

                       SECURITIES AND EXCHANGE COMMISSION
                             WASHINGTON, D.C. 20549

                                    FORM S-8

                          REGISTRATION STATEMENT UNDER
                           THE SECURITIES ACT OF 1933

                          TRANSKARYOTIC THERAPIES, INC.

             (Exact Name of Registrant as Specified in Its Charter)
DELAWARE                                                            04-3027191
(State or Other Jurisdiction of                                           (I.R.S. Employer
Incorporation or Organization)                                            Identification No.)

         195 ALBANY STREET                                                      02139
     CAMBRIDGE, MASSACHUSETTS
(Address of Principal Executive Offices)                                      (Zip Code)
2001 NON-OFFICER, NON-DIRECTOR STOCK INCENTIVE PLAN
                            (Full Title of the Plan)

                                RICHARD F SELDEN
                      PRESIDENT AND CHIEF EXECUTIVE OFFICER
                                195 ALBANY STREET
                            CAMBRIDGE, MASSACHUSETTS
                     (Name and Address of Agent For Service)
                                  617-340-0200
          (Telephone Number, Including Area Code, of Agent For Service)

                         CALCULATION OF REGISTRATION FEE
====================================================================================================================
Title of Securities to be                            Proposed Maximum       Proposed Maximum
Registered                       Amount to be       Offering Price Per     Aggregate Offering        Amount of
                                  Registered               Share                 Price           Registration Fee
--------------------------------------------------------------------------------------------------------------------
Common Stock, $0.01 par
value per share (including    2,000,000 shares     $15.835(1)             $31,670,000(1)        $7,918
the associated Preferred
Stock Purchase Rights)
====================================================================================================================
(1)      Estimated solely for the purpose of calculating the registration fee
         pursuant to Rules 457(c) and 457(h) of the Securities Act of 1933, as
         amended, and based upon the average of the high and low prices of the
         Registrant's Common Stock as reported on the Nasdaq National Market on
         April 25, 2001.

===============================================================================
PART I
              INFORMATION REQUIRED IN THE SECTION 10(A) PROSPECTUS

         ITEM 1. PLAN INFORMATION.

         The information required by Item 1 is included in documents sent or
given to participants in the plan covered by this registration statement
pursuant to Rule 428(b)(1) of the Securities Act of 1933, as amended (the
"Securities Act").

         ITEM 2. REGISTRANT INFORMATION AND EMPLOYEE PLAN ANNUAL INFORMATION.

         The written statement required by Item 2 is included in documents sent
or given to participants in the plans covered by this registration statement
pursuant to Rule 428(b)(1) of the Securities Act.

                                     PART II
               INFORMATION REQUIRED IN THE REGISTRATION STATEMENT

         ITEM 3. INCORPORATION OF DOCUMENTS BY REFERENCE.

         The registrant is subject to the informational and reporting
requirements of Sections 13(a), 14, and 15(d) of the Securities Exchange Act of
1934, as amended (the "Exchange Act"), and in accordance therewith files
reports, proxy statements and other information with the Securities and Exchange
Commission (the "Commission"). The following documents, which are on file with
the Commission, are incorporated in this registration statement by reference:

         (a) The registrant's latest annual report filed pursuant to Section
13(a) or 15(d) of the Exchange Act or the latest prospectus filed pursuant to
Rule 424(b) under the Securities Act that contains audited financial statements
for the registrant's latest fiscal year for which such statements have been
filed.

         (b) All other reports filed pursuant to Section 13(a) or 15(d) of the
Exchange Act since the end of the fiscal year covered by the document referred
to in (a) above.

         (c) The description of the securities contained in the registrant's
registration statement on Form 8-A and filed under the Exchange Act, including
any amendment or report filed for the purpose of updating such description.

         All documents subsequently filed by the registrant pursuant to Sections
13(a), 13(c), 14 and 15(d) of the Exchange Act, prior to the filing of a
post-effective amendment which indicates that all securities offered hereby have
been sold or which deregisters all securities then remaining unsold, shall be
deemed to be incorporated by reference in this registration statement and to be
part hereof from the date of the filing of such documents. Any statement
contained in a document incorporated or deemed to be incorporated by reference
herein shall be deemed to be modified or superseded for the purposes of this
registration statement to the extent that a statement contained herein or in any
other subsequently filed document which also is or is deemed to be incorporated
by reference herein modifies or supersedes such statement. Any statement so
modified or superseded shall not be deemed, except as so modified or superseded,
to constitute a part of this registration statement.

                                      -1-
ITEM 4. DESCRIPTION OF SECURITIES.

         Not applicable.

         ITEM 5. INTERESTS OF NAMED EXPERTS AND COUNSEL.

         Hale and Dorr LLP has opined as to the legality of the securities being
offered by this registration statement.

         ITEM 6. INDEMNIFICATION OF DIRECTORS AND OFFICERS.

         Article VII of the registrant's Amended and Restated Certificate of
Incorporation provides that no director of the registrant shall be personally
liable for any monetary damages for any breach of fiduciary duty as a director,
except to the extent that the Delaware General Corporation Law prohibits the
elimination or limitation of liability of directors for breach of fiduciary
duty.

         Article VIII of the registrant's Amended and Restated Certificate of
Incorporation provides that a director or officer of the registrant (a) shall be
indemnified by the registrant against all expenses (including attorneys' fees),
judgments, fines and amounts paid in settlement incurred in connection with any
litigation or other legal proceeding (other than an action by or in the right of
the registrant) brought against him by virtue of his position as a director or
officer of the registrant if he acted in good faith and in a manner he
reasonably believed to be in, or not opposed to, the best interests of the
registrant, and, with respect to any criminal action or proceeding, had no
reasonable cause to believe his conduct was unlawful and (b) shall be
indemnified by the registrant against all expenses (including attorneys' fees)
and amounts paid in settlement incurred in connection with any action by or in
the right of the registrant brought against him by virtue of his position as a
director or officer of the registrant if he acted in good faith and in a manner
he reasonably believed to be in, or not opposed to, the best interests of the
registrant, except that no indemnification shall be made with respect to any
matter as to which such person shall have been adjudged to be liable to the
registrant, unless a court determines that, despite such adjudication but in
view of all of the circumstances, he is entitled to indemnification of such
expenses. Notwithstanding the foregoing, to the extent that a director or
officer has been successful, on the merits or otherwise, including, without
limitation, the dismissal of an action without prejudice, he is required to be
indemnified by the registrant against all expenses (including attorneys' fees)
incurred in connection therewith. Expenses shall be advanced to a director or
officer at his request, provided that he undertakes to repay the amount advanced
if it is ultimately determined that he is not entitled to indemnification for
such expenses.

         Indemnification is required to be made unless the registrant determines
that the applicable standard of conduct required for indemnification has not
been met. In the event of a determination by the registrant that the director or
officer did not meet the applicable standard of conduct required for
indemnification, or if the registrant fails to make an indemnification payment
within 60 days after such payment is claimed by such person, such person is
permitted to petition the court to make an independent determination as to
whether such person is entitled to indemnification. As a condition precedent to
the right of indemnification, the director or officer must give notice of the
action for which indemnity is sought and the registrant has the right to
participate in such action or assume the defense thereof.

         Article VIII of the registrant's Amended and Restated Certificate of
Incorporation further provides that the indemnification provided therein is not
exclusive, and provides that in the event

                                      -2-
that the Delaware General Corporation Law is amended to expand the
indemnification permitted to directors or officers the registrant must indemnify
those persons to the fullest extent permitted by such law as so amended.

         Article VIII, Section 8 of the registrant's By-Laws provides that the
registrant shall indemnify any and all of the registrant's directors or officers
to the fullest extent permitted by the Delaware General Corporation Law.

         Section 145 of the Delaware General Corporation Law provides that a
corporation has the power to indemnify a director, officer, employee or agent of
the corporation and certain other persons serving at the request of the
corporation in related capacities against amounts paid and expenses incurred in
connection with an action or proceeding to which he is or is threatened to be
made a party by reason of such position, if such person shall have 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 any criminal proceeding, if such person
had no reasonable cause to believe his conduct was unlawful; provided that, in
the case of actions brought by or in the right of the corporation, no
indemnification shall be made with respect to any matter as to which such person
shall have been adjudged to be liable to the corporation unless and only to the
extent that the adjudicating court determines that such indemnification is
proper under the circumstances.

         The registrant maintains a general liability insurance policy which
covers certain liabilities of directors and officers of the registrant arising
out of claims based on acts or omissions in their capacities as directors or
officers.

         ITEM 7. EXEMPTION FROM REGISTRATION CLAIMED.

         Not applicable.

         ITEM 8. EXHIBITS.

         The Exhibit Index immediately preceding the exhibits is incorporated
herein by reference.

         ITEM 9. UNDERTAKINGS.

         1. ITEM 512(a) OF REGULATION S-K. 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;

                      (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. Notwithstanding the foregoing, any
         increase or decrease in volume of securities offered (if the total
         dollar value of securities offered would not exceed that which was
         registered) and any deviation from the low or high end of the estimated
         maximum offering range may be reflected in the form of prospectus filed
         with the Commission pursuant to Rule 424(b) if, in the aggregate, the

                                       -3-
changes in volume and price represent no more than 20 percent change in
         the maximum aggregate offering price set forth in "Calculation of
         Registration Fee" table in the effective registration statement; and

                       (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 (i) and (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
         Section 15(d) of the Exchange Act that are incorporated by reference in
         this 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.

         2. ITEM 512(b) OF REGULATION S-K. The undersigned registrant hereby
undertakes that, for purposes of determining any liability under the Securities
Act, each filing of the registrant's annual report pursuant to Section 13(a) or
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.

         3. ITEM 512(h) OF REGULATION S-K. Insofar as indemnification for
liabilities arising under the Securities 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 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.

                                      -4-
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-8 and has duly caused this registration
statement to be signed on its behalf by the undersigned, thereunto duly
authorized, in Cambridge, Massachusetts, on this 1st day of May, 2001.

                                    TRANSKARYOTIC THERAPIES, INC.

                                    By:  /s/ Richard F Selden
                                         --------------------------------------
                                         Richard F Selden
                                         President and Chief Executive Officer

                        POWER OF ATTORNEY AND SIGNATURES

         We, the undersigned officers and directors of Transkaryotic Therapies,
hereby severally constitute and appoint Richard F Selden, Daniel E. Geffken and
Michael J. Astrue and each of them singly, our true and lawful attorneys with
full power to them, and each of them singly, to sign for us and in our names in
the capacities indicated below, the registration statement on Form S-8 filed
herewith and any and all subsequent amendments to said registration statement,
and generally to do all such things in our names and on our behalf in our
capacities as officers and directors to enable Transkaryotic Therapies, Inc. to
comply with the provisions of the Securities Act of 1933, as amended, and all
requirements of the Securities and Exchange Commission, hereby ratifying and
confirming our signatures as they may be signed by our said attorneys, or any of
them, to said registration statement and any and all amendments thereto.

         Pursuant to the requirements of the Securities Act of 1933, this
registration statement has been signed by the following persons in the
capacities and on the dates indicated.
SIGNATURE                              TITLE                                DATE
/s/ Richard F Selden                  President, Chief Executive                    May 1, 2001
---------------------------           Officer and Director (Principal
Richard F Selden                      executive officer)

/s/ Daniel E. Geffken                 Senior Vice President, Finance                May 1, 2001
---------------------------           and Chief Financial Officer
Daniel E. Geffken                     (Principal financial and
                                      accounting officer)

/s/ Rodman W. Moorhead, III           Director                                      May 1, 2001
---------------------------
Rodman W. Moorhead, III

/s/ Jonathan S. Leff                  Director                                      May 1, 2001
---------------------------
Jonathan S. Leff

                                      -5-
/s/ William R. Miller                 Director                                      May 1, 2001
---------------------------
William R. Miller

/s/ Walter Gilbert                    Director                                      May 1, 2001
---------------------------
Walter Gilbert

/s/ James E. Thomas                   Director                                      May 1, 2001
---------------------------
James E. Thomas

/s/ Wayne P. Yetter                   Director                                      May 1, 2001
---------------------------
Wayne P. Yetter
-6-
INDEX TO EXHIBITS
NUMBER                       DESCRIPTION
------                       -----------
4.1(1)                       Amended and Restated Certificate of Incorporation of the Registrant

4.2(2)                       Certificate of Amendment of Amended and Restated Certificate of the Registrant

4.3(2)                       Certificate of Designation, Number, Voting Powers, Preferences and Rights of
                             Series A Convertible Preferred Stock of the Registrant

4.4(3)                       Certificate of Designations of Series B Junior Participating Preferred Stock
                             of the Registrant

4.5(3)                       Second Amended and Restated By-Laws of the Registrant

4.6(4)                       Rights Agreement dated December 13, 2000 between the Registrant and EquiServe
                             Trust Company, N.A., as rights agent

5.1                          Opinion of Hale and Dorr LLP, counsel to the Registrant

23.1                         Consent of Hale and Dorr LLP (included in Exhibit 5.1)

23.2                         Consent of Ernst & Young, LLP

24.1                         Power of attorney (included on the signature pages of this registration
                             statement)
------------

(1)      Previously filed with the Securities and Exchange Commission as an
         Exhibit to the Registrant's Quarterly Report on Form 10-Q for the
         quarter ended September 30, 1996 (File No. 0-21481) and incorporated
         herein by reference.

(2)      Previously filed with the Securities and Exchange Commission as an
         Exhibit to the Registrant's Quarterly Report on Form 10-Q for the
         quarter ended June 30, 2000 (File No. 0-21481) and incorporated herein
         by reference.

(3)      Previously filed with the Securities and Exchange Commission as an
         Exhibit to the Registrant's Annual Report on Form 10-K for the year
         ended December 31, 2000 (File No. 0-21481) and incorporated herein by
         reference.

(4)      Previously filed with the Securities and Exchange Commission as an
         Exhibit to the Registrant's Current Report on Form 8-K dated as of
         December 14, 2000 and incorporated herein by reference.