Twenty-two human sarcomas were grafted subcutaneously into nude mice. Twelve tumors grew successfully. Nine of these 12 tumors had an aneuploid DNA content, whereas only 1 of 10 nonsuccessful tumors was aneuploid. The 12 sarcomas included two leiomyosarcomas, two malignant schwannomas, one synovial sarcoma, and seven malignant fibrous histiocytomas (MFHs). With light and electron microscopic and immunolabeling studies the original and xenografted tumors (the latter for at least two generations) were histopathologically compared. The xenografted leiomyosarcomas showed ultrastructurally a more pronounced leiomyodifferentiation, and one of the malignant schwannomas a more pronounced schwannian differentiation. The second malignant schwannoma and the synovial sarcoma, however, remained unchanged. Five storiform pleomorphic MFHs expressed features that were not observed in the original tumors. Tumor cells of three of these xenografted sarcomas showed leiomyogenic differentiation (filamentous densities, pinocytotic vescicles, and desmin immunoreactivity), whereas cells of the two others demonstrated schwannian differentiation (long cytoplasmic processes, basal lamina). A xenografted myxoid MFH and a pleomorphic MFH gave rise to pleomorphic sarcomas composed of undifferentiated cells. It appeared that under transplantation conditions tumor cells of storiform pleomorphic MFH can differentiate into various directions.