Mammalian pregnancy is a unique immunological paradox because the fetus, which bears paternal histocompatible antigens which are alien to the maternal immune system can survive normally as an allograft in the mother. Several mechanisms have been proposed to explain fetal acceptance including nonspecific suppression of maternal immunity (1). Previous studies have suggested that factors in pregnant sera play a role in the suppression of maternal immunity (2-9), including sex hormones (2, 3), serum-blocking antibody (4), pregnancy-associated proteins (5), a-fetoprotein (6, 7), and as yet undefined factors. However, none of these have been established as a major factor in the suppressed maternal immunity. Moreover, contradictory results have been recently reported by Smith (8) and Hamilton and Hellstr/Sm (9), who claim that sera from syngeneically or allogeneically pregnant mice do not inhibit the responses of normal lymphocytes to alloantigens. The reasons for these discrepancies are unclear. Other evidence which suggests suppressed maternal immunity during pregnancy includes depressed mixed lymphocyte reactions (10), diminished mitogen responses (6, 11), decreased leukocyte migration (12), and delayed skin graft rejection (13). An increased frequent occurrence of severe viral infection during pregnancy (14) has also been postulated to be related to suppressed maternal immunity. There have, however, been very few reports investigating the antibody response following challenge in pregnant animals. One study (15) reports that the circulating antibody titers to several antigens including sheep erythrocytes (SRBC) t were not significantly altered during pregnancy while we have previously reported a decreased splenic plaque-forming-cell (PFC) response following in vivo immunization of pregnant mice (7).The present study shows that in vitro IgM antibody synthesis against SRBC is decreased in the pregnant spleen cells compared to controls, and moreover this appears to be mediated by nonspecific splenic suppressor cells. At least two populations of pregnant spleen cells were shown to exert a nonspecific suppressor effect. One is a T lymphocyte and the other a nylon wool-adherent cell present in the B-cell-enriched macrophage-depleted fraction. Pregnant spleen cells cultured in vitro secrete soluble supernate factors which decrease the primary IgM antibody response of normal spleen cells. We were unable to demonstrate suppressor cells in the pregnant lymph node