The actin immunophenotype of eight benign mesenchymal tumors, 14 nonsarcomatoid tumors, and 46 sarcomatoid tumors was studied, using monoclonal antibodies (MoAb) specific for alpha-smooth muscle actin (clone 1A4), alpha- and gamma-smooth muscle actin (designated CGA7), and muscle actin (designated HHF35) on frozen sections. Tumor cells of nonsarcomatoid tissues were not reactive, but all leiomyomas and five of the seven leiomyosarcomas reacted with the three MoAbs. One leiomyosarcoma was immunoreactive for the MoAb 1A4 only. One of the six malignant schwannomas showed staining for muscle actin (HHF35). The 22 malignant fibrous histocytomas (MFH) expressed these actin isoforms in various degrees. One case immunoreacted with all three MoAbs, three reacted with 1A4 only, seven reacted with CGA7 and HHF35, and two reacted with HHF35 only. Nine MFHs were not immunoreactive for any of the MoAbs specific for (smooth) muscle and actin. In addition, the expression of desmin and collagen type IV was investigated for the group of leiomyosarcomas and MFHs. Desmin was found in five leiomyosarcomas and in two MFHs. Collagen type IV was seen in all leiomyosarcomas, and was seen weakly in a few small areas in four MFHs. When we take into account the expression of all markers tested [( smooth] muscle actin, desmin, and collagen type IV), then six of the 22 MFHs were unreactive for all these markers. Five of these six tumors were located intramuscularly, whereas only half of the total number of MFH cases had an intramuscular location. The fact that 15 of 22 MFHs displayed one or more markers linked with (smooth) muscle differentiation suggests that some of the MFHs may be classified as poorly differentiated leiomyosarcomas, and that MFH is not a unique entity.