Forty patients with metastatic breast cancer who had received no previous cytotoxic therapy were treated with a combination chemotherapy program CMF (P), which included methotrexate, 60 mg/m2, and 5-fluorouracil, 700 mg/m2, intravenously on the first and eighth days, in addition to cyclophosphamide, 100 mg/m2, and prednisone, 40 mg/m2, by mouth daily from the first to the fourteenth day of a 28-day cycle. Only 2 of 25 patients responded to hormonal therapy or endocrine ablation. Twenty-seven of the 40 patients (68%) had a complete response (8 patients) or partial response (19 patients). Lung, soft tissue, and nodal metastases were the most responsive sites. The median duration of antitumor response was 8 months, with a median survival of 18 months for the responding group. The nonresponders had a median survival of 4 months. The toxicity was primarily hematologic and was especially severe in patients with functional liver impairment due to metastatic disease.