4'-epi-adriamycin was administered intravenously on an every-3-week schedule to 34 patients with advanced malignant tumors. Patients were treated at five dosage levels, ranging from 40 mg/m2 to 100 mg/m2. Hematologic toxicity was dose limiting. No cardiac, renal, or hepatic toxicity was observed; there were no drug-related deaths. Partial alopecia developed in all patients receiving a cumulative dose of 200 mg/m2; mild nausea and vomiting occurred in 13 patients. Although major therapeutic responses were not seen in this phase I trial, 2 of 15 patients with objectively measurable disease showed minor responses; 7 patients had stabilization of previously progressing cancer for 3 to 5+ months. A dose of 85 mg/m2 of epi-Adriamycin every 3 weeks seems an appropriate initial dose for phase II studies in patients having a performance status of 70 or higher. A starting dose of 70 mg/m2 is recommended for patients having a lower performance status.