One hundred and ten patients with stage IV breast cancer were treated with five-drug chemotherapy consisting of prednisone, cyclophosphamide, 5-fluorouracil, methotrexate, and vincristine. Sixty-four percent of 97 evaluable patients achieved a remission, with a median duration of 9 months. Age, disease-free interval, and menopausal status did not affect response to chemotherapy. Patients with visceral dominant site of disease tended to have a lower response rate compared to those with bone or soft tissue dominant site of disease. Remission rate was similar in hormone-responsive and -resistant tumors, although median duration of remission was longer in the former group (11 versus 9 months; P less than 0.05). Median survival from onset of metastasis was much longer in patients who had responded to previous endocrine therapy than those who had failed (53 versus 23 months; P less than 0.0005). Thirty-four percent of the 59 patients who were subsequently treated with Adriamycin after either relapse or failure with combination chemotherapy obtained further palliation, with a median duration of 4 1/2 months. We conclude that cytotoxic chemotherapy is effective in hormone-responsive and -resistant tumors. Sequential endocrine therapy and chemotherapy offer long-term survival to patients with hormone-responsive tumors.