Samples were taken from the human chorionic sac at 6 wk postconception and were stained with monoclonal antibodies to trophoblast and to HLA antigens by means of an indirect immunoperoxidase technique. Antibody to HLA A, B, C antigens did not stain chorionic villous trophoblast in accordance with previous studies, but did stain nonvillous trophoblast of the cytotrophoblast cell columns and cytotrophoblastic shell. Antibody to HLA DR antigens showed no staining of trophoblast. This is the first demonstration of HLA antigens on a human fetal tissue in direct maternal contact. We have discussed the immunologic implications of this finding.