Monoclonal antibodies were used in an investigation of the histogenesis of malignant fibrous histiocytoma (MFH), a neoplasm with morphologic features of both fibroblastic and histiocytic differentiation. In 4 cases of MFH studied, the tumor cells were found to react uniformly with antibodies to determinants expressed on monocyte macrophages (T-200, Ia, MoS-1, MoS-39, MoR-17). Both spindle and histiocyte-like tumor cells expressed these markers. In contrast, in 8 non-MFH soft tissue tumors, tumor cell reactivity was not observed. The reactivity of the spindle cells of MFH for determinants of monocyte/macrophages favors their origin from tissue histiocytes (facultative fibroblasts). The results support the view that MFH is a tumor of the mononuclear phagocyte system.