Amonafide, a benzisoquinoline-1.3-dione was administered to 38 patients with recurrent or metastatic. bidimensionally measurable endometrial cancer. There were 34 patients with no prior cytotoxic chemotherapy, performance status of 0–2, and normal bone marrow, renal, and hepatic function were eligible for response and toxicity evaluation. Amonafide, 300 mg/m2, was administered intravenously over 1 hour daily for 5 consecutive days. Courses were repeated every 21 days. The major grade 3 or 4 toxicities were hematologic with granulocytopenia in 18 patients (53%). thrombocytopenia in 6 patients (18%), and anemia in 8 patients (24%). Infectious complications occurred in 3 patients (9%). Other side effects included cardiac dysrhythmias. hypotension, pain and phlebitis at the site of injection, nausea, vomiting, and flu-like symptoms. The overall objective response rate was 6% (95% confidence interval of 1–20%); 2 patients had a complete response (6%), 9 patients had stable disease (26%) and 21 patients had progressive disease (62%). Two patients had insufficient follow-up for response determination and are assumed to be nonresponders. The median survival of the eligible patients was 8 months. With the toxicity observed and the low response rate, amonafide at this dose and schedule has no efficacy in the treatment of endometrial cancer.