ABSTRACT: The expression of transplantation antigens by cells of the placenta was examined by immunohistological and immunoprecipitation procedures with defined conventional and monoclonal antisera to beta2-microglobulin, DR and DC gene products, and H-Y antigen. Cells of the mesenchymal stroma within chorionic villi were positive by immunofluorescence for major histocompatibility complex antigens, and in male pregnancies for H-Y antigen, but the trophoblast was consistently negative for all antigen systems examined. Immunohistological examination of viable suspensions of cultured diploid trophoblast and of isolated membranes also gave negative results, and after radioiodination and solubilization of membranes, no detectable radioactive material was immunoprecipitated. These results provide further evidence that transplantation antigens are not expressed by human trophoblast. Since this is a fetal structure exposed directly to immunologically competent cells of the mother in the intervillous spaces, this observation may be relevant to the apparent lack of damaging maternal immune responses directed against the fetal homograft.