We treated 39 women with newly diagnosed stage IV breast cancer with a new regimen of mitoxantrone 18 mg/m² on days 1, 29, 57, vincristine 1.4 mg/m² (maximum 2.0 mg) on days 1, 8, 15, 22, 29, 36, 43, 50, and 5-fluorouracil 375 mg/m² on days 15–20, 43–47, 71–75 with leucovorin modulation 500 mg/m² before each 5FU infusion (MVF). This regimen was utilized as an initial cytoreductive or induction program for these patients prior to high-dose intensification with autologous stem cell rescue. Ten patients (25%) obtained a clinical complete response and six patients (15%) obtained a partial response for an overall response rate of 40%. In addition, 10 patients had evaluable disease that was improved or stable (primarily bone and/or bone marrow metastases) after MVF induction. Thus, 26 patients (65%) were eligible for high-dose intensification with autologous stem cell rescue after MVF induction. Toxicity was primarily a mild mucositis and more commonly peripheral neuropathy. MVF therapy is an active treatment program for metastatic breast cancer but the neurotoxicity makes it difficult to recommend for widespread use.