<PAGE>

                                                      Registration No. 333-76973
================================================================================
                      SECURITIES AND EXCHANGE COMMISSION
                             WASHINGTON, DC 20549
                                _______________

                              Amendment No. 2 to
                                   FORM S-3
            REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933
                                _______________

                                MATRITECH, INC.
            (Exact Name of Registrant as Specified in Its Charter)

            Delaware                                            04-2985132
   (State or other Jurisdiction                              (I.R.S. Employer
   of Incorporation or Organization)                      Identification Number)

                               330 Nevada Street
                               Newton, MA 02460
                                (617) 928-0820
   (Address, Including Zip Code, and Telephone Number, Including Area Code,
                 of Registrant's Principal Executive Offices)

                               Stephen D. Chubb
                     President and Chief Executive Officer
                                MATRITECH, INC.
                               330 Nevada Street
                               Newton, MA 02460
                                (617) 928-0820
 (Name, Address, Including Zip Code, and Telephone Number, Including Area Code,
                             of Agent for Service)

                                   Copy to:
                              Rufus C. King, Esq.
                        TESTA, HURWITZ & THIBEAULT, LLP
                                125 High Street
                         Boston, Massachusetts  02110
                                (617) 248-7000
                                _______________

       Approximate Date of Commencement of Proposed Sale to the Public:
As soon as practicable after this registration statement becomes effective.

       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, as amended, 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>

The information contained in this prospectus is not complete and may be changed.
We may not sell these securities until the registration statement filed with the
Securities and Exchange Commission is effective.  This prospectus is not an
offer to sell these securities and it is not soliciting an offer to buy these
securities in any state where the offer or sale is not permitted.




                  Subject to Completion:  Dated June 21, 1999

                                MATRITECH, INC.
                               3,094,965 Shares
                                of Common Stock
                           $.01 Par Value Per Share
                                ---------------



       This prospectus covers the resale of up to 3,094,965 shares of our common
stock by the selling securityholders listed inside.

       Our common stock is quoted on the Nasdaq National Market under the symbol
"NMPS." On June 16, 1999, the last reported sale price for the common stock as
reported by the Nasdaq National Market was $1.1875 per share. Our executive
offices are located at 330 Nevada Street, Newton, Massachusetts 02460, and our
telephone number is (617) 928-0820.



See "Risk Factors" beginning on page 1 for information that should be considered
                               before investing.

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


       Neither the Securities and Exchange Commission nor any state securities
commission has approved or disapproved of these securities or determined if this
prospectus is truthful or complete. Any representation to the contrary is a
criminal offense.

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


                The date of this prospectus is         , 1999.
                                               ----- --
<PAGE>

                            ----------------------
                               TABLE OF CONTENTS
                            ----------------------
<TABLE>
<CAPTION>
                                                                           Page
<S>                                                                        <C>
Matritech, Inc.............................................................  3
Risk Factors...............................................................  3
Use of Proceeds............................................................ 10
Selling Securityholders.................................................... 11
Plan of Distribution....................................................... 12
Legal Matters.............................................................. 13
Experts.................................................................... 13
Where You Can Find More Information........................................ 14
Documents Incorporated by Reference........................................ 14
</TABLE>

                                      -2-
<PAGE>

                                MATRITECH, INC.

     Matritech develops, manufactures and markets innovative cancer diagnostic
products based on its proprietary nuclear matrix protein technology. The nuclear
matrix, a three-dimensional protein framework within the nucleus of cells, plays
a fundamental role in determining cell type by physically organizing the
contents of the nucleus, including DNA. Matritech has demonstrated that there
are differences in the types and amounts of nuclear matrix proteins found in
cancerous and normal tissue. Matritech believes that the detection of these
differences in nuclear matrix proteins, often called NMPs, provides important
diagnostic information about cellular abnormalities, including cancer. Using its
proprietary nuclear matrix protein technology and expertise, Matritech has
developed non-invasive or minimally invasive cancer diagnostic tests for bladder
and colon cancer and is developing additional tests for cervical, breast and
prostate cancer.

                                 RISK FACTORS

     An investment in the shares involves a high degree of risk. This prospectus
contains forward-looking statements which involve risks and uncertainties. Our
actual results could differ materially from those anticipated in these forward-
looking statements as a result of certain factors, including the risks described
below and elsewhere in this prospectus. The following risk factors should be
considered carefully along with the detailed information in this prospectus and
in the documents referred to in this prospectus. These risks, among others, if
realized, could materially hurt our business, results of operations and
financial condition.


     If we are unsuccessful in obtaining needed additional capital, we may be
unable to conduct our business as planned, to pursue desirable markets for our
current products or to develop and market new products.

     We will need additional funding to continue to market our NMP22(R) Bladder
Cancer Test Kit, to conduct research and development, to conduct clinical trials
and to manufacture and market our products as we currently contemplate. We are
currently seeking to raise additional capital and will consider various
financing alternatives, including equity or debt financings and corporate
partnering arrangements. However, we may not be able to raise needed capital on
terms that are acceptable to us, or at all. If we do not receive additional
financing, we may be required to curtail further our expenses or take other
steps that could hurt our future performance. We believe that the combination of
the proceeds from the private placement completed in April 1999 and our existing
capital will be sufficient to fund our operations at least through the end of
1999.

     Because our stock price may be volatile, the shares held by you may lose
their value rapidly.

     The market price of our common stock has been, and may continue to be,
highly volatile. This price has ranged between $3.38 and $0.63 in the fifty-two
week period prior to May 31, 1999. The stock market has from time to time
experienced extreme price and volume fluctuations, particularly in the
biotechnology sector, which have often been unrelated to the operating
performance of particular companies. Factors such as announcements of
technological innovations or new products by our competitors or disappointing
results by third parties, as well as market conditions in our industry, may
significantly impact the market price of our common stock. For example, in the
past our stock price has been affected by announcements of clinical results,
clinical or technical breakthroughs or earnings by other biotechnology companies
unrelated to us or our performance. Our stock price has also been

                                      -3-
<PAGE>

affected by announcements of developments at Matritech. For example, our stock
price has, in the past, reacted to announcements regarding a delay of our
regulatory approval process for a new product, fluctuating sales results and
decreasing balances of funds in the corporate treasury. Thus, as a result of
events at Matritech or in our industry, shares of Matritech stock could lose
their value rapidly.

     Our common stock may be delisted from the Nasdaq National Market, which
would make it more difficult for you to sell shares.

     Our common stock is currently listed on the Nasdaq National Market. For
continued listing of our common stock on the Nasdaq National Market, we must,
among other things, maintain at least $4 million in net tangible assets and a
minimum bid price for our common stock of $1.00. If our net tangible assets fall
below $4 million, or if our common stock trades at a price of less than $1.00
for 30 consecutive business days or more, our shares may be delisted from the
Nasdaq National Market, and trading, if any, would then be conducted in a non-
Nasdaq over-the-counter market. If our shares are delisted, it could be more
difficult to sell them or to obtain accurate price information. In addition, if
our shares are delisted, they may be subject to a rule that imposes additional
sales practice requirements on broker-dealers who sell our shares to persons
other than established customers and accredited investors. For transactions
covered by this rule, the broker-dealer must make a special suitability
determination for the purchaser and must have received the purchaser's written
consent to the transaction prior to sale. Consequently, delisting, if it
occurred, may reduce the ability of broker-dealers to sell our shares and your
ability to sell your shares.

     If we are unable to market and develop our products, we will continue to
incur operating losses and investors may lose interest in our shares and their
market value may fall.

     We have incurred operating losses since we began operations in 1987. These
losses have resulted principally from costs incurred in research and development
and from selling, general and administrative costs associated with our
development. These costs have exceeded our revenues, which to date have been
generated primarily from initial sales of our NMP22 Bladder Cancer Test Kit, our
development agreements, government grants and interest income. We expect to
incur continuing operating losses in the near term. Our ability to be profitable
depends in part on our ability to market our existing products, obtain required
regulatory approvals and develop new products. We may not be able to market
successfully our existing products, obtain required regulatory approvals or
develop, commercialize, produce and market our future products or achieve or
maintain profitability.

     If our NMP22 Bladder Cancer Test Kit does not achieve wide market
acceptance, we will not have significant near-term product sales or revenues.

     We expect to generate substantially all of our near-term product sales from
the sale of our NMP22 Bladder Cancer Test Kits, which were approved for sale in
the United States by the FDA in 1996 and approved for sale in Japan in 1998. Our
results of operations may suffer if the NMP22 Bladder Cancer Test Kit does not
achieve wide market acceptance because NMP22 is our only source of sales
revenue. The remainder of our products still require FDA approval or are in
development and do not result in significant revenues.

     If our distributors do not successfully sell our products, our sales
revenue will suffer.

     We have limited internal marketing and sales resources and personnel. We
derive a significant portion of our sales revenue from distribution agreements
with two distributors. Konica Corporation has

                                      -4-
<PAGE>

an exclusive right to sell our NMP22 Bladder Cancer Test Kit in Japan. Fisher
Diagnostics has a co-exclusive right with us to sell our NMP22 Bladder Cancer
Test Kit to hospitals and commercial laboratories in the United States. Because
we do not deal directly with customers when selling through distributors, we
depend on the ability of Konica and Fisher to market actively, to forecast
demand accurately and to maintain appropriate levels of inventory. We have
minimal control over our distributors, and these distributors are under no
obligation to purchase a minimum quantity of our products. The failure or delay
by a distributor in selling our products, or any material breach of their
agreements with us could significantly reduce our revenues. We may be unable to
enter into additional distribution relationships on favorable terms, if at all.
These events could reduce anticipated future sales growth.

     Our operating results may fluctuate, which makes it difficult to plan our
expense levels and causes operating results to vary significantly.

     Our future operating results may vary significantly from quarter to quarter
or from year to year for several reasons, including:

     .  the timing and size of orders from customers and distributors;

     .  regulatory approvals and the introduction of new products by us; and

     .  market acceptance of our products.

   Our current planned expense levels are based in part upon expectations about
future revenue.  Consequently, operating results may vary significantly from
quarter to quarter or year to year based on the timing of revenue.  Revenue or
profits in any period will not necessarily indicate results in subsequent
periods.

     We face intense competition and our technology may become obsolete.

     Although we are not aware of any other company using nuclear matrix protein
technology to develop diagnostic or therapeutic products, competition in the
development and marketing of cancer diagnostics and therapeutics, using a
variety of technologies, is intense. Many pharmaceutical companies,
biotechnology companies, public and private universities and research
organizations actively engage in the research and development of clinical cancer
diagnostic products. Many of these organizations have greater financial,
manufacturing, marketing and human resources than we do.

     We expect that certain of our clinical tests will compete with existing
FDA-approved clinical tests, including a test known as BTA, which has been
approved for monitoring bladder cancer, a test known as CEA, which is used
primarily for monitoring colorectal and breast cancers, a test known as PSA,
which is used primarily for monitoring and screening prostate cancer, and a test
known as TRUQUANT BR RIA, which is used for monitoring breast cancer. We are
also aware of a number of companies exploring the application of oncogene
technology to cancer diagnostics. Our diagnostic products will also compete with
more invasive or expensive procedures such as surgery, bone scans, magnetic
resonance imaging and other in vivo imaging techniques. In addition, other
companies may introduce competing diagnostic products based on other
technologies that may adversely affect our competitive position. As a result,
our products may become obsolete or non-competitive.

                                      -5-
<PAGE>

     If we are unable to develop and market future products, our sales revenue
may not meet expectations and our stock price may drop.

     Other than the NMP22 Bladder Cancer Test Kit, all of our products are under
development and are not expected to be commercially available in the United
States for some time. The majority of our products under development will
require significant additional research and development, laboratory testing,
clinical testing and regulatory approval prior to commercialization. The
development of our products involves the use of advanced technical methods that
require both a high degree of skill and judgment in their application. We may
encounter unexpected technical difficulties in the course of the development
process that we may be able to overcome only if we expend additional funds and
time, if at all. We may not successfully complete our product development
efforts, and we may not obtain the required regulatory approvals. In addition,
any future products, if and when introduced, may not be successfully
commercialized, produced and marketed or achieve customer acceptance. We believe
that the market value of our stock is based in part on an expectation of future
revenue producing products. If we are unable to develop and market future
products, or if the market believes that we are experiencing difficulty
developing future products, our stock price may drop. For example, the market
reacted negatively when we announced that one of our products would not receive
expedited FDA review.

     Government regulation could adversely make the development and sale of our
products costly and difficult.

     The FDA and, in some instances, foreign governments, extensively regulate
the medical devices that we market and manufacture. The FDA regulates the
clinical testing, manufacture, labeling, distribution and promotion of medical
devices in the United States. If we fail to comply with the FDA's requirements,
including Good Manufacturing Practices, we may face a number of consequences,
including:

     .  fines;

     .  injunctions;

     .  civil penalties;

     .  recall or seizure of products;

     .  total or partial suspension of production;

     .  failure of the government to grant premarket clearance or premarket
        approval for devices;

     .  withdrawal of marketing approvals; and

     .  criminal prosecution.

     The FDA also has the authority to request repair, replacement or refund of
the cost of any device that we manufacture or distribute.

     Any products that we manufacture or distribute in accordance with FDA
clearances or approvals are subject to pervasive and continuing regulation by
the FDA, including:

                                      -6-
<PAGE>

     .  device users are required to comply with recordkeeping requirements and
        to report adverse experiences with the use of the device;

     .  device manufacturers are required to register their establishments and
        list their devices with the FDA and are subject to periodic inspections
        by the FDA and certain state agencies; and

     .  devices are required to be manufactured in accordance with Good
        Manufacturing Practices regulations which impose certain procedural and
        documentation requirements on us with respect to manufacturing and
        quality assurance activities.

     Labeling and promotional activities are subject to scrutiny in the United
States by the FDA and, in certain instances, by the Federal Trade Commission.
For example, the NMP22 Bladder Cancer Test Kit has received FDA approval and may
be promoted by us only as a prognostic indicator. The FDA actively enforces
regulations prohibiting the promotion of devices for unapproved uses and the
promotion of devices for which premarket clearance or approval has not been
obtained. Consequently, we cannot currently promote the NMP22 Bladder Cancer
Test Kit for cancer screening in the United States or for any other unapproved
use. If we fail to comply with these requirements, we may face regulatory
enforcement action by the FDA that would prevent us from manufacturing or
selling our products, hurt our ability to conduct testing necessary to obtain
market clearance for these products and reduce our potential sales revenues.

     We are also subject to a variety of state laws and regulations in those
states or localities where our products are or will be marketed. Any applicable
state or local regulations may hinder our ability to market our products in
those states or localities. Manufacturers are also subject to numerous federal,
state and local laws relating to such matters as safe working conditions,
manufacturing practices, environmental protection, fire hazard control, and
disposal of hazardous or potentially hazardous substances. We may be required to
incur significant costs to comply with these laws and regulations now or in the
future, which could increase future losses or reduce future profitability.

     If we lose our proprietary technology advantage, we could be overwhelmed by
competitors.

     We rely on a combination of patent, trade secret and trademark laws,
nondisclosure and other contractual provisions and technical measures to protect
the proprietary rights in our current and planned products. These protections
may be inadequate, and our competitors may independently develop technologies
that are substantially equivalent or superior to our technology. Patent law
relating to the scope of claims in the biotechnology field is still evolving
and, therefore, the degree of future protection for our proprietary rights is
uncertain. In addition, the laws of certain countries in which our products are
or may be licensed or sold do not protect our products and intellectual property
rights to the same extent as the laws of the United States.

     We believe that the use of the patents for nuclear matrix protein
technology licensed to us and the use of our trademarks and other proprietary
rights do not infringe upon the proprietary rights of third parties. However, we
may not prevail in any challenge of third-party intellectual property rights,
and third parties may successfully assert infringement claims against us in the
future. In addition, we may be unable to acquire licenses to any of these
proprietary rights of third parties on reasonable terms.

                                      -7-
<PAGE>

     Healthcare reform measures and third-party reimbursement policies could
limit the per-product revenues for our products.

     Our ability to commercialize successfully our planned products will depend
in part on the extent to which reimbursement for the cost of our products will
be available from government health administration authorities, private health
insurers and other third-party payors. In the case of private insurers, the
reimbursement of any medical device, either approved for investigational use
only or for research use, is at the sole discretion of the patient's individual
carrier. Even if a procedure has been previously approved for reimbursement, the
insurance carrier may decide not to continue to reimburse the procedure.
Further, even if in the future we do successfully sell our products to managed
care providers, it is possible that these sales will involve significant pricing
pressure on our products and keep our per-product revenues low. Healthcare
reform is an area of continuing national attention and a priority of many
governmental officials. Certain reform proposals, if adopted, could impose
limitations on the prices we will be able to charge in the United States for our
products or the amount of reimbursement available for our products from
governmental agencies or third-party payors. While we cannot predict whether any
of these legislative or regulatory proposals will be adopted or the effect that
these proposals may have on our business, the announcement or adoption of these
proposals could hurt our business by reducing demand for our products and could
hurt our stock price because of investor reactions.

     If we do not develop a larger marketing and sales force, we will remain
dependent on distributors, and we may fail to increase sales.

     We have limited internal marketing and sales resources and personnel. In
order to market successfully our current and future products in the United
States and other territories in which we do not, or do not intend to, use third-
party distributors, we will need to develop a larger marketing and sales force
with appropriate technical expertise and distribution capability. We may be
unable to establish the marketing and sales capabilities that we need, and we
may be unsuccessful in gaining market acceptance for any of our products.

     If we are unable to manufacture the product volumes we need, we will be
unable to achieve profitability.

     We have been manufacturing and assembling our test kits for limited
commercial sales since 1995 but have not yet manufactured the large product
volumes necessary for us to achieve profitability. We may encounter difficulties
in scaling up production of new products, if necessary, including problems
involving:

     .  production yields;

     .  quality control and assurance;

     .  component supply; and

     .  shortages of qualified personnel.

     These problems could make it very difficult to produce sufficient product
to satisfy customer needs and could result in customer dissatisfaction. We may
not be able to achieve reliable, high-volume manufacturing at a commercially
reasonable cost. In addition, numerous governmental authorities

                                      -8-
<PAGE>

extensively regulate our manufacturing operations. Failure to satisfy our
manufacturing needs could result in decreased sales, loss of market share and
potential loss of certain distribution rights.

     If our suppliers cancel their agreements with us, it may be difficult for
us to find replacements for our suppliers.

     We currently rely on sole suppliers for certain key components for our test
kits. If the components from these suppliers should become unavailable for any
reason, we would seek alternative sources of supply. In order to maintain the
FDA validation of our manufacturing process, we would have to show that these
alternative sources of supply are equivalent to our current sources. Although we
attempt to maintain an adequate level of inventory to provide for these and
other contingencies, if our manufacturing processes are disrupted as a result of
a shortage of key components or a revalidation of new components, we may be
unable to meet our commitments to customers. Our failure or delay in meeting our
commitments could cause sales to decrease, market share to be lost permanently,
and could result in significant expenses to obtain alternative sources of supply
with the necessary facilities and know-how.

     If we are unable to retain our key personnel, we may be unable to achieve
our developmental objectives.

     Our success depends, in large part, upon our ability to attract and retain
a highly qualified scientific and management team. We have no employment
contracts with any of our key personnel. The loss of key personnel or the
failure to recruit the necessary additional personnel needed for a qualified
team might impede the achievement of developmental objectives. We face
competition for qualified personnel from other companies, research and academic
institutions, government entities and other organizations. We may not be
successful in hiring or retaining qualified scientific or management personnel
on acceptable terms, given the competition among numerous pharmaceutical and
biotechnology companies, government entities and research and academic
institutions for qualified personnel.

     If we are sued for product related liabilities, the cost could be
prohibitive to us.

     The testing, marketing and sale of human healthcare products entail an
inherent exposure to product liability, and third parties may successfully
assert product liability claims against us. Although we currently have insurance
covering our products, we may not be able to maintain this insurance at
acceptable costs in the future, if at all. In addition, our insurance may not be
sufficient to cover large claims. Significant product liability claims could
result in large and unexpected expenses as well as a costly distraction of
management resources and potential negative publicity and reduced demand for our
product.

     Our activities involve the use of hazardous materials, and we may be held
liable for any accidental injury from these hazardous materials.

     Our research and development activities involve the controlled use of
hazardous materials, including radioactive compounds. Although we believe that
our safety procedures for handling and disposing of our hazardous materials
comply with the standards prescribed by federal, state and local laws and
regulations, the risk of accidental contamination or injury from these materials
cannot be completely eliminated. In the event of an accident, we could be held
liable for damages that result and significant and unexpected costs including
costs relating to liabilities and clean-up, costs from

                                      -9-
<PAGE>


increased insurance premiums or inability to obtain adequate insurance at a
reasonable price and costs from loss of operations during clean-up.

     Some of our computer systems and software products may not properly
recognize dates after December 31, 1999, which could disrupt our
operations.

     We rely upon microprocessor-based personal computers and commercially
available applications software. Some existing computer systems and software
products do not properly recognize dates after December 31, 1999, the Year 2000
problem. The Year 2000 problem could result in miscalculations, data corruption,
system failures or disruptions of operations. We are subject to potential Year
2000 problems affecting our computer systems, our internal systems and the
systems of our material suppliers or service vendors, any of which could have a
material adverse effect on our business, financial condition and results of
operations. Based on our assessments to date, we anticipate that our critical
systems, including our computer network, telephone system, air ventilation
system and security system, will be Year 2000 compliant by early in the fourth
quarter of 1999. We do not anticipate that we will incur material expenses to
make these systems Year 2000 compliant.

     Year 2000 errors or defects in the internal systems maintained by our
material suppliers or service vendors could require us to incur unanticipated
expenses to remedy any problems or replace affected suppliers or vendors.
To date, we have identified key suppliers and vendors and have requested
information with regard to Year 2000 compliance. We are currently formulating
contingency plans to address problems that may arise if we fail to address our
Year 2000 problems in a timely fashion or if our material suppliers and vendors
fail to address their Year 2000 problems in a timely fashion. We may be unable
to address all our Year 2000 problems in a timely fashion, and the Year 2000
issues of third parties may result in costly expenditures by us. [The SEC would
like us to consider the impact upon Matritech's business and operations if the
worst case scenario with regard to the year 2000 problem were to occur.]


                                USE OF PROCEEDS

     Matritech will receive no part of the proceeds from the sale of any of the
shares by any of the selling securityholders.

                                      -10-
<PAGE>

                            SELLING SECURITYHOLDERS

     The following table sets forth certain information as of June 16, 1999 with
respect to the shares of common stock of Matritech held by each selling
securityholder. The shares may be offered from time to time by any of the
selling securityholders or by those individuals and entities to whom they may
transfer or distribute the shares. See "Plan of Distribution."

     The persons and entities named in the table below have sole voting and
investment power with respect to all shares shown as beneficially owned by them
based upon information provided to Matritech by the selling securityholders.

     In calculating the number of shares beneficially owned by each selling
securityholder after the offering, we have assumed that the selling
securityholders will sell all of the shares of common stock of Matritech
registered under this prospectus. The selling securityholders may sell all or
any part of their shares registered under this prospectus.

     In calculating the percentage of shares beneficially owned by each selling
securityholder prior to and after the offering, we have based our calculations
on the number of shares of common stock deemed outstanding as of June 16, 1999.
As of June 16, 1999, the number of shares of common stock deemed outstanding
includes 21,724,217 shares of common stock. None of the selling securityholders
owns any options, warrants or other convertible securities which are exercisable
or convertible into common stock within 60 days of June 16, 1999.

<TABLE>
<CAPTION>
------------------------------------------------------------------------------------------------------------
                                              Number of                                   Number of Shares
                                     Shares Beneficially Owned           Number of       Beneficially Owned
                                           Prior to Offering           Shares Offered      After Offering
                                      ------------------------         --------------   --------------------

Name                                  Number           Percent                          Number       Percent
----                                  ------           -------                          ------       -------
<S>                               <C>              <C>               <C>             <C>           <C>
Grethe R. Bruckner                         40,000         *                  20,000     20,000          *
A.B. Siemer                               749,384       3.5%                749,384          0          *
Zero Stage Capital VI                   2,325,581      10.7%              2,325,581          0          *
Limited Partnership
TOTAL                                   3,114,965                         3,094,965
------------------------------------------------------------------------------------------------------------
</TABLE>
* Less than 1%

     Stephen D. Chubb, Chairman and Chief Executive Officer of Matritech, is a
limited partner of Zero Stage Capital VI Limited Partnership. To the best of our
knowledge, none of the other selling securityholders had any material
relationship with Matritech or any of its affiliates within the three-year
period ending on the date of this prospectus.

                                      -11-
<PAGE>

                             PLAN OF DISTRIBUTION

     The shares of common stock of Matritech offered under this prospectus may
be sold from time to time by or for the account of any of the selling
securityholders or by those individuals and entities to whom they pledge,
donate, distribute or transfer their shares or other successors in interest.

     The selling securityholders bought the shares of common stock offered under
this prospectus from Matritech in a private placement completed on April 6,
1999. Matritech will not receive any of the proceeds from the sale of these
shares by the selling securityholders. Matritech is paying the expenses of
registering these shares for offer and sale by the selling securityholders,
other than selling commissions and the fees and expenses of their counsel or
other advisors. Matritech has agreed to indemnify the selling securityholders
against certain liabilities, including liabilities under the Securities Act of
1933, and the Securities Exchange Act of 1934.

     The distribution of the shares of common stock of Matritech offered under
this prospectus by the selling securityholders is not subject to any
underwriting agreement. The shares may be sold under this prospectus directly to
purchasers by the selling securityholders in negotiated transactions; by or
through brokers or dealers in ordinary brokerage transactions or transactions in
which the broker solicits purchasers; block trades in which the broker or dealer
will attempt to sell the shares as agent but may position and resell a portion
of the block as principal; transactions in which a broker or dealer purchases as
principal for resale for its own account; or through underwriters or agents.
The shares of common stock of Matritech offered under this prospectus may be
sold at a fixed offering price, which may be changed, at the prevailing market
price at the time of sale, at prices related to the prevailing market price or
at negotiated prices. Any brokers, dealers, underwriters or agents may arrange
for others to participate in any of these transactions and may receive
compensation in the form of discounts, commissions or concessions from the
selling securityholders and/or the purchasers of the shares. Each selling
securityholder will be responsible for payment of any and all commissions to
brokers. Matritech has agreed to indemnify the selling securityholders against
certain liabilities, including liabilities under the Securities Act and the
Exchange Act.

     The selling securityholder may also loan or pledge the shares registered
under this prospectus to a broker-dealer and the broker-dealer may sell the
shares so loaned or upon a default the broker-dealer may effect sales of the
pledged shares using this prospectus.

     In connection with the private placement which was completed on April 6,
1999, Matritech executed certain subscription agreements with the selling
securityholders in which Maritech has agreed, at its expense, to file the
registration statement to which this prospectus is a part and to take certain
other actions to permit the selling securityholders to sell the shares of common
stock of Matritech offered under this prospectus under the Securities Act and
applicable state securities laws.

     In order to comply with the securities laws of individual states, if
applicable, the shares of common stock of Matritech offered under this
prospectus will be sold in those jurisdictions only through registered or
licensed brokers or dealers. In addition, in certain states these shares may not
be sold unless they have been registered or qualified for sale in the applicable
state or an exemption from the registration or qualification requirement is
available and is complied with.

     If and when any of the shares covered by this prospectus qualifies for sale
under Rule 144 under the Securities Act, they may be sold under Rule 144 rather
than under this prospectus.

                                      -12-
<PAGE>


     Any selling securityholder and any broker-dealer, agent or underwriter that
participates with the selling securityholder in the distribution of the shares
of common stock of Matritech offered under this prospectus may be considered to
be "underwriters" within the meaning of the Securities Act, in which event any
commissions received by those broker-dealers, agents or underwriters and any
profit on the resale of the shares purchased by them may be considered to be
underwriting commissions or discounts under the Securities Act.

     The selling securityholders are not restricted as to the price or prices at
which they may sell the shares of common stock of Matritech offered under this
prospectus. Sales of shares at less than the market price may depress the market
price of Matritech's securities. Moreover, the selling securityholders are not
restricted as to the number of shares which may be sold at any one time, and it
is possible that a significant number of shares could be sold at the same time
which may also depress the market price of Matritech's securities.

     Under applicable rules and regulations under the Exchange Act, any person
engaged in the distribution of the shares of common stock of Matritech offered
under this prospectus may not simultaneously engage in market making activities
with respect to the shares for a period of time prior to the commencement of the
distribution. In addition, each selling securityholder will be subject to
applicable provisions of the Exchange Act and the rules and regulations under
the Exchange Act, including, but not limited to, Rule 10b-5 and Regulation M,
which provisions may limit the timing of purchases and sales of the shares by
the selling securityholder.

     There is no assurance that any selling securityholder will sell any or all
of the shares described in this prospectus and may transfer, devise or gift
these securities by other means not described in this prospectus.

     Expenses of preparing and filing the registration statement and all post-
effective amendments will be borne by Matritech.

     Matritech is permitted to suspend the use of this prospectus in connection
with sales of the shares of common stock of Matritech offered under this
prospectus by holders during periods of time under certain circumstances
relating to pending corporate developments and public filings with the
Securities and Exchange Commission, the Commission, and similar events.

                                 LEGAL MATTERS

     Several legal matters with respect to the shares of common stock of
Matritech offered under this prospectus will be passed upon for Matritech by
Testa, Hurwitz & Thibeault, LLP, Boston, Massachusetts.

                                    EXPERTS

     The financial statements of Matritech as of December 31, 1997 and 1998 and
the three years in the period ending December 31, 1998, incorporated by
reference in this prospectus and elsewhere in this registration statement have
been audited by Arthur Andersen LLP, independent public accountants, as
indicated in their reports with respect to Matritech's financial statements, and
are included in this prospectus in reliance upon the authority of Arthur
Andersen LLP as expected in giving these reports.

                                      -13-
<PAGE>

                      WHERE YOU CAN FIND MORE INFORMATION

     Matritech is subject to the informational requirements of the Exchange Act,
and in accordance with those requirements files reports, proxy statements and
other information with the Securities and Exchange Commission. The reports,
proxy statements and other information that Matritech files with the SEC under
the informational requirements of the Exchange Act may be inspected and copied
at the public reference facilities maintained by the Commission at Judiciary
Plaza, Room 1024, 450 Fifth Street, N.W., Washington, D.C. 20549, and at the
following regional offices of the Commission: Seven World Trade Center, 13th
Floor, New York, New York 10048 and Citicorp Center, 500 West Madison Avenue,
Suite 1400, Chicago, Illinois 60611-2511. Copies of these materials can also be
obtained from the Public Reference Section of the Commission at 450 Fifth
Street, N.W., Washington, D.C. 20549 at prescribed rates. Please call 1-800-SEC-
0330 for information about the SEC's Public Reference Room. Matritech's common
stock is traded on the Nasdaq National Market, and the reports, proxy statements
and other information that Matritech files with the SEC may also be inspected at
the offices of The Nasdaq Stock Market, Inc., Reports Section, 1735 K Street,
N.W., Washington, D.C. 20006.

     The Commission also maintains a Web site that contains reports, proxy and
information statements and other information regarding registrants that file
electronically with the Commission. The address of the Commission's Web site is
http: //www.sec.gov.

     Matritech has filed with the Commission a registration statement on
Form S-3, including all amendments to the registration statement under the
Securities Act with respect to the shares of common stock of Matritech offered
under this prospectus. This prospectus does not contain all of the information
set forth in the registration statement, certain parts of which are omitted in
accordance with the rules and regulations of the Commission. For further
information regarding Matritech and the shares offered under this prospectus,
please see the registration statement and to the exhibits and schedules filed
with the registration statement. Statements contained in this prospectus
regarding the contents of any agreement or other document filed as an exhibit to
the registration statement are not necessarily complete, and in each instance
please see the copy of the full agreement filed as an exhibit to the
registration statement. We qualify each of these statements in all respects by
the reference to the full agreement. The registration statement, including the
exhibits and schedules to the registration statement, may be inspected at the
public reference facilities maintained by the Commission at 450 Fifth Street,
N.W., Washington, D.C. 20549 and copies of all or any part of the registration
statement may be obtained from the Commission's office upon payment of the
prescribed fees.

                      DOCUMENTS INCORPORATED BY REFERENCE

     The SEC allows Matritech to "incorporate by reference" the information we
file with them, which means that we can disclose important information to you by
referring you to those documents. The following documents filed by Matritech
with the Commission, File No. 001-12128, are incorporated by reference in this
prospectus, except as superseded or modified by this prospectus:

1.  Matritech's annual report on Form 10-K for the fiscal year ended
    December 31, 1998, filed under the Exchange Act, which contains audited
    financial statements for the fiscal year ended December 31, 1998.

2.  Matritech's current report on From 8-K dated April 7, 1999.

                                      -14-
<PAGE>


3.  The description of Matritech's common stock, $.01 par value per share,
    contained in the section entitled "Description of Registrant's Securities to
    be Registered" contained in Matritech's registration statement on Form 8-A
    filed with the Commission on March 10, 1992, including any amendment or
    report filed for the purpose of updating the description of Matritech's
    common stock.

     All documents filed by Matritech under Sections 13(a), 13(c), 14 or 15(d)
of the Exchange Act after the date of this prospectus and prior to the
termination of the offering made under this prospectus are incorporated by
reference in this prospectus and made a part of this prospectus from the date
Matritech files the documents with the SEC. Any statement contained in this
prospectus or in a document incorporated or deemed to be incorporated by
reference in this prospectus shall be deemed to be modified or superseded for
purposes of this prospectus to the extent that a statement contained in this
prospectus or in any other subsequently filed document which also is or is
deemed to be incorporated by reference in this prospectus 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 prospectus.
Matritech will provide without charge to each person to whom this prospectus is
delivered, upon the written or oral request of that person, a copy of any
document incorporated in this prospectus by reference other than exhibits unless
those exhibits are specifically incorporated by reference into the documents.
Requests for these copies should be directed to Matritech, Inc., Attention:
Robert W. Morgan, 330 Nevada Street, Newton, Massachusetts 02460, telephone
(617) 928-0820.

                                      -15-
<PAGE>

================================================================================
You should rely only on the information contained          3,094,965 Shares
 in this prospectus or information specifically
 incorporated by reference in this prospectus.  We                of
 have not authorized anyone to provide you with
 information that is different.  Neither the                 Common Stock
 delivery of this prospectus, nor any sale made
 hereunder, shall create any implication that the                 of
 information in this prospectus is correct after
 the date hereof.  This prospectus is not an offer          MATRITECH, INC.
 to or solicitation of any person in any
 jurisdiction in which such offer or solicitation
 is illegal.
<TABLE>
<CAPTION>
          ----------------------------
               TABLE OF CONTENTS
          ----------------------------
<S>                                <C>
   Matritech, Inc. ................  3
   Risk Factors ...................  3
   Use of Proceeds ................ 10
   Selling Security holders ....... 11
   Plan of Distribution ........... 12
   Legal Matters .................. 13
   Experts ........................ 13
   Where You Can Find More
   Information .................... 14
   Documents Incorporated by
   Reference ...................... 14
</TABLE>
================================================================================
                                         , 1999
                                ----- ---
<PAGE>

                                    PART II

                    INFORMATION NOT REQUIRED IN PROSPECTUS

Item 14.  Other Expenses of Issuance and Distribution.

     The expenses incurred by the Company in connection with the issuance and
distribution of the securities being registered are estimated as follows:
<TABLE>
<CAPTION>
                                                         Amount
                                                       ----------
<S>                                                    <C>

Securities and Exchange Commission registration fee..  $ 1,102.00
Nasdaq Additional Listing fee........................  $17,500.00
Legal fees and expenses..............................  $28,000.00
Accounting fees and expenses.........................  $ 2,500.00
Miscellaneous........................................  $ 3,000.00
                                                       ----------
 Total...............................................  $52,062.00

</TABLE>

     None of the above expenses will be paid by the Selling Securityholders.

Item 15.  Indemnification of Directors and Officers.

     Pursuant to the provisions of Section 145 of the Delaware General
Corporation Law ("DGCL") the Company has the power to indemnify certain persons,
including its officers and directors, under stated circumstances and subject to
certain limitations, for liabilities incurred in connection with services
performed in good faith for the Company or for other organizations at the
request of the Company.

     Article Seventh of the Company's Amended and Restated Certificate of
Incorporation provides that no director of the Company shall be liable for
monetary damages for breach of fiduciary duty, except to the extent that the
DGCL prohibits the elimination of liability of directors for breach of fiduciary
duty.

     Article Twelfth of the Company's Amended and Restated Certificate of
Incorporation provides that a director or officer of the Company (a) shall be
indemnified by the Company 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 Company) brought against him by virtue of his position as a director or
officer of the Company 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 Company, 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 Company
against all expenses (including attorneys' fees) and amounts paid in settlement
incurred in connection with any action by or in the right of the Company brought
against him by virtue of his position as a director or officer of the Company 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 Company, except that no indemnification
shall
<PAGE>

be made with respect to any matter as to which such person shall have been
adjudged to be liable to the Company, 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 Company 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.

     Article Twelfth of the Company's Amended and Restated Certificate of
Incorporation further provides that the indemnification provided therein is not
exclusive and provides that in the event that the DGCL is amended to expand or
limit the indemnification permitted to directors or officers, the Company must
indemnify those persons to the fullest extent permitted by such law, as so
amended.

     In addition to the indemnification provided by Section 145 of the DGCL, the
Company has entered into an Indemnity Agreement with each of its directors
pursuant to which the Company agrees to indemnify that director for (1) all
expenses, liabilities, judgments, fines and amounts paid in settlement actually
and reasonably incurred in connection with any legal action, suit or proceeding
against the director by reason of the fact that he was an agent of the Company
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 Company, and with respect to any criminal
proceedings had no reasonable cause to believe his conduct was unlawful, and (2)
all expenses incurred in connection with the investigation, defense, settlement
or appeal of any legal action or proceeding brought against the director by or
in the right of the Company by reason of any action taken or not taken by him in
his capacity as a director of the Company 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 Company. The Company is not obligated under the terms of the Indemnity
Agreements to indemnify its directors (a) for expenses or liabilities paid
directly to the directors by directors' and officers' insurance, (b) on account
of any claims against the directors for an accounting of profits made from the
purchase or sale by directors of securities of the Company pursuant to Section
16(b) of the Exchange Act, as amended, (c) if indemnification would not be
lawful.

Item 16.  Exhibits.

<TABLE>
<CAPTION>
Exhibit No.  Description of Exhibit
-----------  ----------------------
<C>          <S>
   4.1       Specimen Common Stock Certificate (filed as Exhibit 4.2 to the
             Company's Registration Statement No. 33-46158 on Form S-1 and
             incorporated herein by reference).

   4.4       Form of Subscription Agreement between the Company and the several
             purchasers (filed as Exhibit 10.17 to the Company's Annual Report
             on Form 10-K for the fiscal year ended December 31, 1998 and
             incorporated herein by reference).

   5.1       Opinion of Testa, Hurwitz & Thibeault, LLP.*

  23.1       Consent of Arthur Andersen LLP.*

  23.2       Consent of Testa, Hurwitz & Thibeault, LLP
             (contained in Exhibit 5.1).*

  24.1       Power of Attorney (included on page II-5 of the Registration
             Statement).*
</TABLE>
______________________________
*  Filed herewith.

                                      II-2
<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.
               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 changes in volume and price represent no more than 20 percent
               change in the maximum aggregate offering price set forth in the
               "Calculation of Registration Fee" table in the effective
               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;

     (2) That, for the purpose of determining any liability under the Securities
         Act of 1933, 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 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
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.

(c)  Insofar as indemnification for liabilities arising under the Securities Act
of 1933 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

                                      II-3
<PAGE>

Exchange Commission such indemnification is against public policy as expressed
in the Securities Act of 1933 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 of 1933 and will be governed by the final adjudication of such
issue.

                                      II-4
<PAGE>

                                  SIGNATURES

     Pursuant to the requirements of the Securities Act of 1933, as amended, 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
registration statement to be signed on its behalf by the undersigned thereunto
duly authorized, in the City of Newton, Commonwealth of Massachusetts, on
June 18, 1999.

                                  Matritech, Inc.

                                  By:  /s/ Stephen D. Chubb
                                       ----------------------
                                       Stephen D. Chubb
                                       Director, Chairman and Chief Executive
                                       Officer


                                  SIGNATURES

     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/ Stephen D. Chubb         Director, Chairman and Chief        June 18, 1999
--------------------         Executive Officer (Principal
Stephen D. Chubb             Executive Officer)


/s/ David L. Corbet          Director, President and Chief       June 18, 1999
--------------------         Operating Officer
David L. Corbet


/s/ Robert W. Morgan         Vice President and Chief            June 18, 1999
--------------------         Financial Officer (Principal
Robert W. Morgan             Financial and Accounting
                             Officer)


         *                   Director                            June 18, 1999
--------------------
J. Robert Buchanan


         *                   Director                            June 18, 1999
--------------------
David Rubinfien


         *                   Director                            June 18, 1999
--------------------
Richard A. Sandberg


         *                   Director                            June 18, 1999
--------------------
T. Stephen Thompson


         *                   Director                            June 18, 1999
--------------------
C. William Zadel
</TABLE>

* By Power of Attorney

                                      II-5
<PAGE>

                                 EXHIBIT LIST

<TABLE>
<CAPTION>
Exhibit No.       Description of Exhibit
-----------       ----------------------
<C>               <S>
    4.1           Specimen Common Stock Certificate (filed as Exhibit 4.2 to the
                  Company's Registration Statement No. 33-46158 on Form S-1 and
                  incorporated herein by reference).

    4.4           Form of Subscription Agreement between the Company and the
                  several purchasers (filed as Exhibit 10.17 to the Company's
                  Annual Report Form 10-K for the fiscal year ended December 31,
                  1998 and incorporated herein by reference).

    5.1           Opinion of Testa, Hurwitz & Thibeault, LLP**

   23.1           Consent of Arthur Andersen LLP**

   23.2           Consent of Testa, Hurwitz & Thibeault, LLP (contained in
                  Exhibit 5.1)**

   24.1           Power of Attorney **
</TABLE>
_______________________________
** Previously filed.