Amonafide (AMF), NSC 308847 is an investigational anticancer drug acting as a DNA intercalating agent. This paper presents results of a phase II clinical study of AMF in disseminated malignant melanoma. Twenty patients, eleven males and nine females, with biopsy proven malignant melanoma, performance status 0-2; median age 59 (range 29-74), and no previous chemotherapy, were treated with AMF 300 mg/m2/day by 60 min i.v. infusion for five days repeated every three weeks. Fifteen patients had lung (9 patients) and/or liver (8 patients) involvement. None had known brain metastasis at entry. All 20 patients were evaluated for response and toxicity. Six patients had stable disease and fourteen had increasing disease. With 0/20 responses, the upper 95% confidence limit for the response rate was 14%. The median survival time was 5.7 months. Hematologic toxicity was dose limiting with the incidence of leucopenia 45% and thrombocytopenia 20%. The nonhematologic toxicities included nausea and vomiting (60%), alopecia (20%), headaches (15%), diarrhea (10%), and phlebitis (10%). We conclude that AMF administered at this dose and schedule is not active in the treatment of patients with malignant melanoma, previously untreated with chemotherapy.