Extracts of human decidual tissue obtained in the first trimester of pregnancy showed potent suppressive activity in mixed lymphocyte cultures. These extracts contained substantial amounts of the decidual protein PP14. Purified PP14 also exhibited in vitro immunosuppressive activity, and such activity in decidual extract and purified PP14 preparations was removed by treatment with a monoclonal anti-PP14 antibody-based immunoadsorbent. PP14 was present in seminal plasma, which also exhibited immunosuppressive activity that could be reduced, but not removed, by the immunoadsorbent. PP14 may be an important immunomodulator in the human reproductive system.