A prospective randomized trial was conducted comparing the clinical response of 78 previously untreated patients with advanced metastatic breast cancer to a combination of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) or to a combination of cyclophosphamide, adriamycin, and 5-fluorouracil (CAF). Sixty-two percent of the patients receiving CMF responded to treatment compared to an 82% response rate for the patients receiving CAF. Although within acceptable limits, hematologic and GI toxicity was greater with CAF. There was no significant difference in the duration of response to the two regimens. Therefore, the therapeutic difference between the two therapies is a higher initial response rate to the adriamycin containing regimen.