Six-year results of a prospective, randomized clinical trial of three treatment regimens [(1) cytoxan, methotrexate and 5-fluorouracil (CMF); (2) CMF plus the antiestrogen drug, tamoxifen (CMFT); (3) CMFT plus Bacillus Calmette-Guerin (BCG) vaccinations] in 312 women with stage II breast cancer are reported. Addition of tamoxifen to CMF therapy significantly decreased the number of recurrences at 6 years in ER + patients with greater than or equal to 4 positive axillary lymph nodes, and in those with tumor diameter in excess of 3 cm. The beneficial effect of tamoxifen appeared to be independent of the menopausal status. Addition of tamoxifen to CMF had no effect on disease-free survival in ER + patients with 1-3 positive axillary lymph nodes or in patients with ER--tumors. Addition of BCG vaccinations had no discernible effect on disease-free survival. ER measurements in the primary tumor provide important prognostic information regardless of treatment, with ER + patients having increased overall survival after 6 years. Further follow-up is needed to determine whether tamoxifen is delaying recurrence or preventing it in a subset of these patients.