Therapy with melphalan, 5-fluorouracil (5-FU), and medroxyprogesterone acetate combination (MFP) in women with metastatic or recurrent endometrial carcinoma not amenable to surgery or radiation therapy, as compared to progesterone therapy alone, was evaluated. Previously 114 women with progesterone therapy were treated and achieved a 15.8% objective response rate; 7.0% were complete responders. Thirteen women with documented recurrent or metastatic endometrial carcinoma were entered into the MFP study. Thirteen were evaluable for toxicity and 11 for response (2 had no measurable parameter). Treatment consisted of melphalan 0.2 mg/kg per day for 4 days every 4 wk, 5-FU 15 mg/kg per day for 4 days every 4 wk and medroxyprogesterone acetate 1.0 g i.m. weekly. Two of the first 3 patients treated with this regimen developed severe thrombocytopenia (platelets, 25,000 and 17,000/mm3). The remaining 10 patients received 5-FU at a dose of 10 mg/kg per day for 4 days every 4 wk. Except for 1 patient who developed thrombophlebitis, there was no other significant toxicity in the 90 courses of therapy received by the 13 women. Of the 11 women evaluable for response, 6 (54.5%) responded (2 complete responders, 4 partial responders), 2 had stationary disease and 3 progressed after having had stationary disease for 3, 6 and 9 mo., respectively. Of special interest was that the 2 women with adenosquamous carcinoma responded and 1 additional patient with adenocarcinoma maintained a complete response with 5-FU therapy alone.