To define optimal regional treatment as initial management of locally advanced (Stage III & IV) breast cancer, 509 patients treated from 1966-1982 were reviewed. All patients received comprehensive postoperative irradiation of the peripheral lymphatics and chest wall, following surgical procedures varying from incisional biopsy to classical radical mastectomy. Patients were followed from 1 to over 16 years. The survival rate at 5 and 10 years for the entire series is 41% and 26%. Fifty-eight patients having radical surgery for T3 tumors and subsequently found to have negative axillary lymph nodes showed the highest rates of survival, 72% at 5 years and 57% at 10 years. This was significantly better (p less than .01) than patients with T3N+ disease, (5 year survival 44%; 10 year, 29%) and T4N+ disease (44%, 39%). Four hundred seventy patients with non-inflammatory carcinoma and no supraclavicular metastases were considered technically resectable. Three hundred eighty-one of these patients underwent a definitive surgical procedure removing all gross cancer prior to irradiation and, as expected, showed higher rates of local disease control than patients having lesser surgery (79% versus 45%, p less than .01). These patients also showed markedly better rates of survival and relapse-free survival with 50% alive and 38% disease free, versus 14 and 8%, at 5 years (p less than .01). There were no 10 year survivors among the 89 technically resectable patients having less than total gross resection. Long term relapse-free survival of locally advanced breast cancer can be achieved with aggressive combined local-regional therapy. Total resection of all gross cancer prior to irradiation is recommended. Modifications of postoperative radiation therapy techniques are suggested to further improve local control rates for these advanced tumors. This large series provides a baseline for evaluation of current programs adding adjuvant systemic therapy to regional treatment.