A monoclonal antibody, PAL-E, is described that is specific for endothelial cells. The monoclonal antibody, an IgG2a, markedly stains endothelium of capillaries, medium-sized and small veins, and venules in frozen sections of human and some animal tissues tested. It reacts not at all or only weakly with endothelium of large, medium-sized, and small arteries, arterioles, and large veins and does not stain the endothelial lining of lymphatic vessels and sinus histiocytes. The cellular staining pattern and tissue staining were different from those obtained with antifactor VIII R:AG antiserum and Ulex europaeus I lectin. Blocking experiments indicated that these three reagents recognize different endothelial binding sites. Therefore, PAL-E is a new staining reagent for endothelium in frozen sections. Based on immunoelectronmicroscopic observations, the antigenic determinant recognized by PAL-E is associated with endothelial vesicles.