A prospective randomized trial was undertaken to compare the efficacy of a three-drug regimen using cyclophosphamide, methotrexate, and fluorouracil to a five-drug regimen using vincristine sulfate and prednisone in addition to cyclophosphamide, methotrexate, and fluorouracil in advanced breast carcinoma. Seventy-two patients who had received no prior chemotherapy were randomized. Thirty-eight patients received three drugs, and 34 received fivedrug therapy. The objective response rates, 34% and 50%, respectively, did not differ significantly (P =.13). As expected, myelosuppression occurred in most patients, and neurotoxicity was much more common in patients receiving vincristine. Three of 12 patients treated with the fivedrug regimen after progression of disease while receiving the three-drug regimen showed an objective response to the five-drug regimen. (Arch Intern Med 137:1711-1714, 1977)