A randomized trial of the effect of adjuvant CMF chemotherapy in patients with Stage III breast cancer receiving primary local radiation or local radiation plus surgery, failed to reveal a survival benefit from early systemic treatment. The subset of premenopausal patients receiving chemotherapy did, however, show a significant prolongation of disease-free survival from 23 to 55 months. Overall survival of this subgroup was not increased. The study included the use of two dose levels of CMF to assess whether higher chemotherapy doses would be more effective. No dose effect was observed. Initial local control with radiation therapy or radiation plus surgery was achieved in the majority (90.9%). Distal recurrence and death from metastatic disease were the major causes of treatment failure. Treatment benefit among premenopausal patients was mainly delayed onset of distal metastatic disease. Among premenopausal patients, salvage therapy for metastatic disease appeared more effective in those not previously exposed to systemic treatment.