Various drug combinations including Adriamycin have been tested in soft tissue sarcomas, but optimal treatment remains unclear. We have evaluated Adriamycin with and without dimethyl-triazeno-imid-azole-carboxamide (DTIC) in the treatment of Stage III or IV and recurrent sarcomas of the uterus. Two hundred and forty cases of these rare tumors were evaluable. Of 146 evaluable patients with measurable disease, 13/80 (16.3%) of Adriamycin-treated patients and 16/66 (24.2%) of patients receiving the combination showed an objective response (P > 0.05). Lung metastases responded more frequently (P = 0.04) to combination therapy, but there was no survival advantage. For patients with nonmeasurable disease the progression-free interval was similar (10.0 months for Adriamycin and 8.0 months for the combination). Leiomyosarcomas had a significantly longer survival than other cell types (12.1 versus 6.0 months, P < 0.001) but there was no advantage for either regimen. There was a suggestion that heterologous mixed mesodermal sarcomas were more responsive to the combination (27.3 versus 8.7%). The addition of DTIC produced significantly more hematologic and gastrointestinal toxicity. Other Adriamycin combinations should be evaluated in uterine sarcomas.