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Helper and suppressor cells have been identified in lymph nodes of multiparous pregnant mice using one-way mixed lymphocyte reactions. Primiparous C57B1 and C57B1/10ScSn females during pregnancy and immediately post-partum gave unaltered MLR reactivity compared to virgin controls when stimulated with paternal or third-party alloantigens. In contrast, multiparity produced strain-dependent alterations in responsiveness: C57B1 females being hyporesponsive while C57B1/10ScSn mice were hyper-responsive to these antigens. To evaluate regulator activity, the cells were treated with mitomycin C and mixed with normal syngeneic MLR responder populations. Results showed that mixtures of para-aortic and inguinal lymph node cells from pregnant C57B1 females suppressed while those from pregnant C57B1/10ScSn increased normal virgin MLR responses. Treatment of the regulator cells with anti-Thy-1.2 plus complement showed that suppressor activity was predominantly non-T cell in nature while C57B1/10ScSn helper activity was wholly T cell-dependent. The regulator cells appeared to be non-specific since they were found in syngeneically as well as allogeneically mated females but covert specificity could not be totally excluded. Embryo resorption in the C57B1 strain was associated with helper rather than suppressor activity. These results suggest that suppressor cells are not essential for the maintenance of pregnancy and that the presence of regulator cells probably reflects the normal homeostatic mechanisms controlling the maternal immune response to the conceptus. [ABSTRACT FROM AUTHOR]