Of the new anthracycline derivatives, epirubicin is the antibiotic whose antitumor activity is comparable to that of doxorubicin while its cardiotoxicity is reduced by half. We therefore incorporated into our continuing study on anthracycline antitumor effects and toxicity a group of 22 evaluable patients, mean age 52 years, with advanced breast cancer, all of whom had previously undergone chemotherapy, radiotherapy and/or hormonal therapy. Epirubicin was administered at a dose of 120 mg/M2 every 3 weeks, for a maximum of 10 such cycles. The left ventricular ejection fraction (LVEF), determined by radionuclide ventriculography, was measured periodically in all patients. We observed 2 complete responses and 13 partial responses (CP + PR = 69%) of 61 weeks' mean duration; in 3 cases lesions remained stationary while the disease progressed in 4 patients. No patients died of acute toxicity. The main side effects were severe alopecia in 82% of the subjects and moderate degrees of nausea without vomiting in 41%. After 6 treatment cycles, 4 patients showed mild cardiotoxicity and at an epirubicin cumulative dose of 1,200 mg/M2 2 patients developed congestive heart failure (CHF). Hematological toxicity was in no case so severe as to require a reduction in the dose but only a postponement of treatment by 3 to 5 days in 9% of cycles. Without increasing hematological or cardiac toxicity, epirubicin, at a dose of 120 mg/M2, has shown itself to be a highly effective agent against advanced breast cancer.