The interaction between cultured human trophoblast cells and materanl lymphocytes was used as an in vitro model to investigate trophoblast antigenicity. Cytotoxic effects in the trophoblast monolayer were apparent after 72 hr incubation and depended on the presence of non-lymphoid cell types in addition to lymphocytes. Lysis of trophoblast was preceded by blast cell formation and apparently involved close contact between the maternal cells and the trophoblast cells. The nature of the cytotoxic reaction suggested the presence of histocompatibility factors on trypsinized trophoblast cells. This manifestation could be due to removal of fibrinoid or enhancing antibody from the cultured cells. The ability of trypsinized trophoblast cells to synthesize mucoprotein was investigated by the Hale colloidal iron test and found to be unimpaired. The effect of maternal serum on the recognition of human trophoblast antigens by maternal lymphocytes was used as an in vitro model to investigate the occurrence of enhancing antibody in maternal serum. The cytotoxic effects of maternal lymphocytes on trophoblast were completely prevented by the presence of maternal serum, this protective effect being reduced significantly by removal of IgG from the maternal serum. A slight protective effect of allogeneic pregnancy serum was also observed. It is suggested that these findings support a role for immunological enhancement in maintaining the foetal allograft.