There is mounting evidence to suggest that vascular endothelial cell injury plays an important role in the pathogenesis of preeclampsia. In this study an enzyme-linked immunoassay was used to demonstrate increased binding of immunoglobulins G and M to human umbilical vein endothelial cells by sera from women with severe preeclampsia as compared with normal pregnant control women. Fifty percent of women with preeclampsia versus 15.4% of control women had either immunoglobulin G or immunoglobulin M binding. In addition, immunofluorescent staining of normal renal cortical tissue with preeclamptic sera showed increased binding of immunoglobulin G to arterioles in patients with anti-vascular endothelial cell antibodies. These antibodies were not directed at HLA antigens and did not cross react with platelets. Interferon-gamma stimulation did not increase immunoglobulin binding. Antibodies to antigens expressed on vascular endothelial cells may be important in mediating the endothelial damage seen in preeclampsia.