4'-Epi-doxorubicin (4'e-Dx) was used as a single agent in a broad phase II study involving a variety of advanced metastatic tumors. A total of 115 patients were treated, of whom 93 were evaluable. The dosage was 75 mg/m2/cycle repeated every 21 days, with a maximal cumulative dose of 550 mg/m2. Nine responses were achieved in a total of 28 patients with breast cancer (32%). The response rate was 54% in breast cancer patients receiving 4'e-Dx as first-line treatment, 25% in patients previously given chemotherapy without doxorubicin, and 11% in patients previously given chemotherapy with doxorubicin. Some therapeutic activity was also detected in endometrial carcinoma, epidermoid carcinoma of the cervix, non-Hodgkin's lymphoma, melanoma, and skin epidermoid tumor, but the number of patients entered in the study with these various tumors was too limited to allow any statement on efficacy of 4'e-Dx. No treatment schedule with 4'e-Dx had to be interrupted because of toxicity. In a total of 373 evaluable cycles, only three acute reversible ECG abnormalities were recorded. In 16 of 109 evaluable patients there was some minor or moderate alteration of one or more of the three major blood cell parameters following 4'e-Dx therapy, requiring a postponement of the next cycle by less than or equal to 10 days.