Soft tissue sarcomas are generally resistant to most chemotherapeutic agents, and individuals with advanced disease have a poor prognosis. We evaluated amonafide, a new drug that has significant activity against several tumor cell lines, to determine its activity against sarcomas. Amonafide was administered to 18 patients with advanced soft tissue sarcoma (16 of whom had received prior chemotherapy) at a dose of 300 mg/m2 over 60 min daily for 5 days. Courses were repeated every 21 days. Toxicity was mild, but no responses were observed. We conclude that amonafide is not an active agent in previously treated, advanced soft tissue sarcomas in the dose and schedule utilized.