Sixty vascular tumors including 23 angiosarcomas, 300 nonvascular tumors, and selected normal tissues were immunohistochemically evaluated with antibodies to CD31, CD34, and von Willebrand factor (vWF), and monoclonal antibody BNH9, to test the sensitivity and specificity of these markers in the identification of endothelial cells and vascular tumors. Formaldehyde-fixed paraffin-embedded tissues and avidin biotin complex immunostaining were used. All markers labeled normal vascular and lymphatic endothelial cells approximately equally with the exception of CD34 which showed inconsistent expression within the lymphatics. In addition, antibody to CD31 reacted with platelets and megakaryocytes, CD34 with fibroblasts and aortic smooth muscle cells, and BNH9 with many epithelial cells including squamous and gastrointestinal epithelia. Antibody to vWF often showed significant stromal background staining which made the staining occasionally uninterpretable. Benign vascular tumors showed rather uniform staining with all antibodies. However, angiosarcomas were heterogeneous; CD31 was positive in 21/27, CD34 in 25/27 cases, BNH9 in 22/25, and vWF in 18/27 cases. Epithelioid hemangioendotheliomas showed consistent labeling for vWF, but were inconsistently labeled with antibodies to the other markers. Kaposi's sarcoma was positive for both CD31 and CD34. In addition, antibody to CD34 labeled the tumor cells in hemangiopericytoma, cerebellar hemangioblastoma, meningioma, most epithelioid sarcomas, dermatofibrosarcomas, and in a few other sarcomas. CD31, in turn, was not found in sarcomas other than angiosarcomas, but labeled weakly occasional carcinomas and mesotheliomas. Many adenocarcinomas and the glandular component of synovial sarcoma were BNH9 positive.(ABSTRACT TRUNCATED AT 250 WORDS)