Fifty-one patients with advanced breast cancer entered a prospective study of combination chemotherapy, consisting of mitoxantrone (10 mg/m2), methotrexate (30 mg/m2), and vincristine (1 mg/m2, MIMO) given intravenously every 21 days. None of the patients had received prior chemotherapy for metastatic disease, although 24 had been previously given adjuvant chemotherapy. Forty-seven patients were analyzed for response and toxicity. Objective response was observed in 20 of them (42%) with 3 complete responses (6%) stable disease in 7 (15%), and progression in 19 (40%). Best responses were achieved in lung metastases. Liver metastases did not respond. The median duration of response was 9 months and the median time to disease progression 11 months. Toxicity was mild. Nausea and myelotoxicity were the main side effects. MIMO was found to be an effective and well tolerated first-line treatment for advanced breast cancer. The regimen was compared historically with MIMO plus carboplatin. The two types of treatment were found equipotent, with MIMO being less toxic.