The antigenicity of human syncytiotrophoblast membrane (TM) was analyzed using rabbit antiserum raised against TM. From immunoblot analysis, about ten protein bands in TM were recognized by the anti-TM. These included placental alkaline phosphatase and TM-bound albumin. From limited antigenic specificity studies, these antigens, with the exception of albumin, were not detectable in membranes of liver, kidney, heart, and erythrocyte, or in human normal serum. Therefore, these antigens appear to be placental membrane specific. Analysis of lymphocyte membrane by immunoelectrophoresis, crossed immunoelectrophoresis, and immunoblot techniques revealed that a single protein band, designated "40 kDa," was cross-reactive with the anti-TM antiserum, indicating that this antigen is shared commonly between placenta and lymphocyte membranes. Experimental evidence suggesting that the 40-kDa membrane antigen is probably a unique trophoblast-lymphocyte cross-reactive antigen is based on the following observations: the 40-kDa antigen was not detectable in liver, heart, and kidney membrane; beta 2-microglobulin (12,000 daltons) was not detectable in our TM preparation; and the lymphocyte membrane showed only a single protein band at 40,000 daltons, not at 12,000 for beta 2-microglobulin.