Formalin-fixed, paraffin-embedded tissue sections from 26 malignant fibrous histiocytomas (MFH) and 61 benign fibrohistiocytic proliferations (BFHP) were evaluated immunohistochemically. An avidinbiotin-peroxidase technique was used to determine immunoreactivity for alpha-1 antichymotrypsin, muramidase, HLA-DR, leucocyte common antigen, S-100 protein, vimentin, desmin, and keratin. MFHs were consistently positive for ACT and vimentin and inconsistently reactive for the other antigens. MFHs were negative for LCA suggesting a mesenchymal origin for these lesions. In the MFH histologic subtypes, antigen expression was not significantly different to be useful in their classification. Also no distinctive pattern emerged relative to immunoreactivity and tumor location. The benign lesions, giant cell tumor of tendon sheath, dermatofibroma, and oral benign fibrous histiocytoma differed from the MFHs in that they were often LCA positive, suggesting origin from hematopoetic mononuclear-macrophages. The immunoprofiles of peripheral fibromas and "giant cell" fibromas were felt to be consistent with origin from mesenchymal cells. Several of the antigens studied could be used to differentiate the benign lesions studied from other benign neoplasms. The antigens were, however, of little value in separation of benign and malignant lesions.