900 pregnancy sera were screened for monocyte antibodies. 23 sera (2.6%) were found to be reactive with monocytes in an allotypic pattern distinct from blood group ABO, HLA-A,B,C, DR and DQ specificities. Because of strong reactions and high reproducibility, 4 sera with pure endothelial monocyte (EM) reactivity and 2 sera also positive with B lymphocytes of certain donors were selected for population and family studies. The frequency of positive reactions in a panel of 26 random donors obtained with the pure EM sera was 13, 8, 8 and 13% with clearly distinct patterns. Analysis of the tentatively designated EM antigens 1.1, 1.2, 2.1, and 2.2 in 7 families revealed definite segregation with HLA. By means of two crossing-over events within the HLA region the two hypothetical EM loci were localized centromeric of HLA-A and one of both loci centromeric of HLA-B.