To evaluate the role of chemotherapy in local control of primary breast cancer, the incidence of local failure was evaluated in 768 patients treated with surgery and adjuvant, combination chemotherapy that contained fluorouracil, doxorubicin, and cyclophosphamide (FAC) at our institute between 1974 and 1982. Of these patients, 429 received postoperative irradiation (XRT) before adjuvant therapy. A group of 178 historical control patients had mastectomies and received irradiation after surgery without chemotherapy. The rates of locoregional recurrence alone in the three groups were as follows: FAC, 12%; FAC plus XRT, 5%; and XRT, 10%. The difference in recurrence rates between the FAC group and the FAC plus XRT subgroup was significant (P less than 0.01). Local failure rates were evaluated by stage and nodal status; patients with Stage III disease and those with four or more disease-positive nodes had a higher incidence of local failure than did patients with Stage II disease or those who had one to three positive nodes. Systemic chemotherapy and local therapies resulted in 50% local control at the time of locoregional recurrence in patients treated with FAC, whereas local control was achieved in 18% of patients with local recurrence in the XRT subgroups. Overall life-time local control of disease was similar whether irradiation was administered initially (in the period after operation) or at the time of local recurrence. Irradiation after mastectomy remains an integral part of a combined modality approach in selected groups of patients.