Murine lymphoid cells from late (16-20 day) gestational placentae were studied for their ability to respond to mitogens and adult allogeneic cells in the mixed lymphocyte reaction (MLR) and the cell-mediated lympholysis test. Placental lymphocytes from Balb/c mice expressed a weak to moderate proliferative response to concanavalin A (Con A), phytohemagglutinin (PHA), and pokeweed mitogen when compared to the mitogenic responses of adult spleen cells. The stimulatory effects of Con A and PHA were abrogated after depleting the T cells from the placental lymphocyte preparation. Lipopolysaccharide-induced reactivity was similar for both cell populations. In MLR Balb/c placental lymphocytes did not undergo significant DNA synthesis after in-vitro exposure to irradiated C75BL/6 spleen cells, nor were cytotoxic lymphocytes generated against H-2b alloantigens. Lack of an MLR response was not associated with the presence of a suppressor lymphoid-cell population in the placenta. In marked contrast, placental trophoblastic cells were refractory in their responsiveness when cultured with either mitogens or allogeneic cells. These data show that although there is a selective deficiency in the placenta of cells reactive toward alloantigens, limited differentiation of lymphoid cells does occur which may offer immunologic protection to the fetal allograft during embryogenesis.