The nature of the humoral immune response induced in virgin female mice by injections of F1 placental and fetal tissues has been examined and compared to that induced by immunization with F1 adult spleen cells and by multiple allogeneic pregnancy. In a 'responder' strain mouse, as defined by the ability of multiple allogeneic pregnancy to elicit an anti-paternal humoral immune response, both F1 placental and fetal tissues induced the formation of alloantibodies primarily of the IgG1 sub-class, similar to those induced by allogeneic pregnancy, but different from those elicited by adult spleen cells. However, only the placental tissues induced alloantibodies possessing all the characteristics of those appearing in multiparous allogeneic pregnancy. In contrast, the alloantibodies induced by the injected fetal tissue possessed complement-dependent cytotoxic activity, indicating that the inability of pregnancy-induced alloantibodies to mediate cytotoxicity may not be related to their restriction to the IgG1 sub-class. In a 'non-responder' mouse strain, where multiple allogeneic pregnancy does not lead to a maternal alloantibody response, F1 placental tissues, in contrast to fetal and adult tissues, failed to induce a humoral immune response. Injection of F1 placental tissue therefore elicits responses that mimic both the properties and the strain-dependent distribution of the alloantibodies identified in normal murine pregnancy. This implies that the immunogenic stimulus in pregnancy emanates from the placental rather than the fetal compartment of the allogeneic conceptus.