In January, 1972, the Southwest Oncology Group initiated two randomized studies for patients with advanced breast cancer. The study for patients with prior chemotherapy showed a 33% response rate with adriamycin. The study for patients without previous chemotherapy consisted of three treatment regimens; a weekly repeated combination of cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone; these same five drugs given in courses of 5 days repeated every 4 weeks; and adriamycin as a single agent every 3 weeks. For the 283 evaluable patients, the response rates were: weekly combination 63/106 (59%); intermittent combination 39/98 (40%); and adriamycin 31/79 (39%). The median duration of response was 8 months for weekly combination, 10 months for intermittent therapy and only 4 months for adriamycin. Leukopenia was the dose-limiting toxicity with all three regimens. The weekly combination is the most effective therapy for patients with advanced disease. Extensive trails of combinations that include adriamycin are underway.