In a prospective randomized study adjuvant combination chemotherapy with CMF was administered for 12 monthly cycles to 207 patients subjected to radical mastectomy (Halsted or extended) and treatment failure was compared to that observed in 179 patients whose primary therapy consisted only of radical surgery (control group). All patients of both groups had histologically positive axillary lymph nodes. At three years from mastectomy the total failure time distribution was 45.7% in control patients compared to 26.3% in women given CMF (P less than 0.0001). New disease manifestations were higher in the subgroup with four or more nodes (64.9% vs 41.5%) compared to that with one to three nodes (37.9% vs 19.1%). Premenopausal controls showed a progressively higher incidence of treatment failure compared to CMF patients (P=0.00001). The decreased recurrence rate in postmenopausal women given CMF was appreciable only during the first 12 months. From this time on, the difference no longer existed. The cumulative percent of recurrence in patients without or with drug-induced amenorrhea (27.2% vs 9.2%) was not statistically significant. At three years 21.4% of control patients have died of progressive cancer compared to 10.4% of CMF patients. The difference in the survival curves was not significant (P=0.08). Toxicity was moderate and reversible. No drug induced neoplasm was observed. Present results confirm the efficacy of 12 CMF cycles in premenopausal patients. Postmenopausal women probably require a more intensive and prolonged adjuvant chemotherapy.