Normal pericytes were found to express factor XIIIa (F-XIII) and histocompatibility antigen HLA-DR. These markers were studied in 15 hemangiopericytomas (HPC) and 16 other tumors with an HPC-like pattern. A subpopulation of tumor cells expressing F-XIII and HLA-DR antigens was a constant feature of HPC and supported their pericytic origin. Meningeal HPC did not differ in phenotype from peripheral soft tissue HPC. Most tumors with an HPC-like pattern (including synovial sarcomas, malignant schwannomas, leiomyosarcomas, and liposarcomas) were negative for F-XIII and HLA-DR. Malignant fibrous histiocytomas, however, invariably contained a subpopulation expressing these antigens. Therefore, F-XIII can be considered as a marker of fibrohistiocytic differentiation in HPC. Individual tumor cells in HPC occasionally were positive for factor VIII-related antigen (F-VIII-R-Ag), suggesting that the spectrum of differentiation in HPC may include the endothelial cell line. The differentiation characteristics of HPC support the concept that pericytes are primitive cells that may act as precursors to other mesenchymal cells.