OBJECTIVE We asked if the lack of normal trophoblastic invasion of spiral arteries in the basal plate of abnormal pregnancies was associated with the expression of HLA-DR antigens and intercellular adhesion molecules (ICAM-1) on endovascular cytotrophoblasts. METHODS The basal plates of placentae from 15 normal and 55 abnormal pregnancies, including preeclampsia, small-for-gestational age infants, and mothers with history of secondary recurrent spontaneous abortion, were studied immunocytochemically by using monoclonal antibodies to HLA-DR and ICAM-1. Spiral and uteroplacental arteries were identified by using a triple antibody technique with antibodies to cytokeratin, alpha-smooth muscle actin, and von Willebrand factor to detect cytotrophoblasts, arterial smooth muscle cells, and endothelium, respectively. RESULTS Placentae with normal placentation showed the presence of uteroplacental arteries that contained endovascular cytotrophoblasts that were negative for HLA-DR and ICAM-1 antigens. Placentae from abnormal pregnancies showed the presence of spiral arteries without trophoblastic invasion and uteroplacental arteries that were surrounded by numerous macrophages and T lymphocytes. Endovascular cytotrophoblasts in uteroplacental arteries of placentae from abnormal pregnancies reacted with antibodies to HLA-DR and ICAM-1 antigens. CONCLUSIONS Placentae from normal pregnancies show uteroplacental arteries that contain endovascular cytotrophoblasts that do not react with antibodies to ICAM-1 and HLA-DR antigens, and placentae from abnormal pregnancies with uteroplacental arteries that are associated with arteries that do not show physiological changes contain endovascular cytotrophoblasts that react with antibodies to ICAM-1 an HLA-DR antigens. Normal uteroplacental arteries were found to be not surrounded by round cell infiltrates, but uteroplacental arteries associated with arteries that lack physiological changes were surrounded by round cell infiltrates, indicating that round cell infiltrates and endovascular cytotrophoblasts which react with antibodies to ICAM-1 and HLA-DR antigens are associated with abnormal pregnancies. These findings suggest that the cellular infiltrates are associated with endovascular cytotrophoblasts that react with ICAM-1 and HLA-DR antigens.