Combination chemotherapy can produce a rapid and frequent therapeutic effect against advanced endometrial adenocarcinoma regardless of tumor distribution. A new treatment program is described. Melphalan, 5-fluorouracil and medroxyprogesterone acetate achieved 6 or 7 objective responses in patients. This result with combination chemotherapy is substantially better than results with single agents or hormones alone and justifies further evaluation of combinations of cytotoxic chemotherapy as part of the initial treatment of choice for patients with advanced endometrial adenocarcinoma.