Twenty-three cases (12 low grade, 11 high grade) of endometrial stromal sarcoma were studied with monoclonal antibodies to vimentin, keratin, desmin, muscle actin, epithelial membrane antigen, and collagen type IV, using the avidin-biotin immunoperoxidase method. Tumors were highly variable in the expression of these antigens. Some tumors contained both epithelial and smooth muscle-related antigens; others were immunoreactive only for the intermediate filament vimentin. Immunoreactivity patterns for metastases or recurrences were similar to the respective primary tumor and no correlation was observed between tumor grade and antigen expression. Normal myometrium, when present, was keratin-positive and variably epithelial membrane antigen-positive. We conclude that endometrial stromal sarcoma, as well as normal myometrium, may express both epithelial and/or muscle-related antigens. These findings most likely reflect a common mesodermal-mullerian derivation and illustrate the intimate relationship of the endometrial stromal cell to the endometrial glands and myometrium. Knowledge of these immunoreactivity patterns is essential when evaluating poorly differentiated uterine tumors or spindle cell tumors presenting in extrauterine locations.