Thirty consecutive patients with metastatic breast cancer previously untreated by chemotherapy were given high-dose cyclophosphamide (Cytoxan) and high-dose 5-fluorouracil (5-FU) as first-line therapy. Cyclophosphamide, 1200 mg/m2 was administered intravenously (IV) on day 1 and 5-FU, 600 mg/m2 IV on days 1 through 5. Cycles were repeated every 21 days or on hematologic recovery. Twenty-eight of the 30 patients achieved a remission (16 partial, and 12 complete), i.e., a response rate of 93%, and a complete response rate of 40%. The actuarial survival rate at 43 months was 52% for the population as a whole, and 68% for patients who achieved a complete response. Hematologic toxicity was relatively severe and the initial doses had to be reduced by 20% in all patients between the second and fifth courses. No deaths due to either infection or bleeding were seen due largely to intensive supportive care. It is concluded that increasing the doses of a small number of drugs of proven efficacy may be more useful than increasing the number of drugs given in lower doses. Furthermore, this approach spares other effective drugs for second-line therapy.