The Southeastern Cancer Study Group, in a prospectively randomized study involving patients with advanced breast cancer, has compared a low dose intermittently administered five-drug regimen including cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone (CMFVP) with an aggressively administered three-drug regimen including cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF). CAF induced more responses and more complete responses and a longer duration of disease control. However, only a marginal difference was demonstrated in overall survival between the two regimens (p = <0.10). Patients with a good risk pattern of metastases, i.e. those with nodular local chest wall recurrence, nodular pulmonary metastases, or bone-only metastases were more likely to achieve a response and survive longer than those with a poor risk pattern, i.e. lymphangitic pulmonary metastases, pleural effusion with chest wall ulceration, or widespread metastases, including hepatic. All of the differences between the two regimens were noted in the good risk pattern groups. CAF provided no additional benefit to patients presenting with poor risk patterns of metastases. Adriamycin-containing combinations may achieve a greater degree of tumor cell kill in certain subsets of patients with advanced breast cancer, but this provides only a marginal increase in survival. © 1983 Martinus Nijhoff Publishers.