Mitoxantrone (MIX), a member of the anthraquinone chemical class, was found to be a potential anticancer agent. It has a similar spectrum of activity as Adriamycin in experimental and human tumors. Thirty-five female patients with metastatic breast cancer, refractory to previous chemotherapy, were treated between 1986 and 1987 with MIX (14 mg/m2 i.v. every 3 weeks); patients with diffuse bone metastases or heavily pretreated patients received 10–12 mg/m2 MIX. All patients were evaluable for response and toxicity. Two patients achieved complete response and 4 partial response, giving an overall response rate of 17%. Median time of response was 5.5 months. The drug was well tolerated. Objective response was obtained mostly in patients with a performance status (Karnofsky scale) of more than 70%, and in those who received more than 12 mg/m2 MIX per course. One patient developed cardiomyopathy, another an acute myocardial infarction, and 3 patients had pathological changes on echocardiography or multigated nuclear angiography. Hematological and gastrointestinal toxicity was tolerable. We found MIX to be a potentially effective second-line treatment with mild toxicity in patients with metastatic breast cance