The authors have investigated a possible relationship between tumor cells of malignant fibrous histiocytomas (MFHs) and histiocytes. This relationship was studied by means of immunophenotyping using monoclonal antibodies specific for the monocyte cell lineage (FMC-17, Mac-1, OKM-1, Leu-M1, and lysozyme) and mono- and polyclonal antibodies specific for fibroblasts (respectively, FIB-86 and FSG). The immunophenotypes of the MFH tumor cells were compared with those of tumor cells of "true" histiocytic tumors. Monocyte lineage-specific determinants could be demonstrated in varying amounts on cells of the "true" histiocytic tumors but not on cells of MFH or other soft-tissue tumors. The reverse was true for determinants on fibroblasts. The absence of these determinants on malignant histiocytes, and their presence on MFH (and also on benign fibrous histiocytomas, fibrosarcomas, schwannomas, osteosarcomas, hemangiosarcomas, leio- and rhabdomyosarcomas) supported the conclusion that MFH tumor cells originate from mesenchymal cells which do not belong to the mononuclear phagocytic system. Subdivision of the MFH tumors revealed that the storiform-pleomorphic subtypes could express HLA-Dr/Ia antigens, like histiocytic tumors. The inflammatory cell subtype, however, lacked these antigens.