Forty-one women with non-metastatic but locally advanced breast cancer were treated by modified radical or radical mastectomy, and were then randomized to receive one of two adjuvant chemotherapy regimens. Regimen A consisted of 6 months of cyclophosphamide, adriamycin, and fluorouracil (CAF) followed by 6 months of cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone (CMFVP). Regimen B was 12 months of CMFVP. Patients were stratified for estrogen-receptor status, and all patients with a positive estrogen receptor value received tamoxifen 20 mg bid in addition to the chemotherapy. Eight of 21 patients randomized to Regimen A are alive and free of disease, whereas only 1 of 20 patients on Regimen B is well. A trend toward improved disease-free survival favoring Regimen A was observed (P = .05), although a significant difference in overall survival has not been demonstrated. Our findings support the continued study of adriamycin-containing regimens in the adjuvant setting and in combined modality therapy of locally advanced breast cancer.