Summary The study describes the effects of crude extracts of the fetal membranes of day 25 sheep conceptuses and of certain purified protein hormones and pregnancy-associated antigen on the mitogen-induced response of sheep peripheral blood lymphocytes (PBL) in vitro. A dose-dependent suppression of the proliferative response of PBL to phytohaemagglutinin, pokeweed mitogen and concanavalin-A was seen when cultures were supplemented with a soluble extract of fetal membranes. Preliminary characterization suggested that the suppressive agent was heat stable and dialysable. These properties distinguished the immunosuppressive component of membrane extracts from ovine pregnancy-associated antigen, which is heat labile and non-dialysable. However, both high and low molecular weight forms of ovine pregnancy associated antigen were also shown to inhibit lymphocyte transformation in vitro. In contrast, ovine luteinizing hormone, prolactin, growth hormone and human placental lactogen were inactive. The findings are consistent with the hypothesis that immunosuppressive substances are present in the gravid uterus during early pregnancy in the sheep.