This study evaluated mitoxantrone and paclitaxel combination chemotherapy in the treatment of patients with metastatic breast cancer. Thirty-seven patients who had developed progressive disease after prior chemotherapy were treated with mitoxantrone (14 mg/m2) and paclitaxel (150 mg/m2) every 21 days for a maximum of six cycles. The most frequent grade 3 or 4 nonhematological toxicities were fever and nausea. Grade 4 neutropenia occurred in 71% of patients. Cardiotoxicity occurred in 2 patients, both of whom had previously received doxorubicin. Objective response was achieved in 35% of patients (5% complete response and 30% partial response) and 41% had stable disease. Median time to disease progression and median survival were 6 and 12 months, respectively. The percent of patients with an objective response was not different for those who had received prior doxorubicin or had chemotherapy in the preceding 6 months. This regimen appears to be effective and well tolerated as salvage therapy and merits further evaluation.