From 1958 to 1985, 107 patients with a clinical and/or histopathologic diagnosis of non-metastatic inflammatory breast cancer received radiotherapy as all or part of initial treatment. Therapy included definitive irradiation alone in 31 patients, irradiation with mastectomy in 16 patients, irradiation and combination chemotherapy in 23 patients, and irradiation with chemotherapy and surgery in 37 patients. Survivors have a median follow-up of 30 months. Overall median relapse-free survival (RFS) was 12 months (12% at 5 years). Local control and relapse-free survival were significantly improved for patients receiving surgery as part of initial treatment: 19% (10/52) of operated patients experienced locoregional failure vs. 70% (37/53) not operated (p less than 0.0001). The median overall actuarial survival was 24 months (17% at 5 years). Patients who received surgery showed improved survival (44 months vs. 18 months median; 37% vs. 7% at 5 years; p = 0.0004). Chemotherapy also was associated with improved relapse-free survival (18 months vs. 8 months median; 20% vs. 5% at 5 years; p = 0.02) and actuarial survival (32 months vs. 17 months median; 23% vs. 3% at 5 years; p less than 0.02). Patients treated with initial chemotherapy (usually 2-3 cycles of CAF), surgery, and postoperative irradiation followed by maintenance chemotherapy showed a 34 month median relapse-free survival (37% at 5 years RFS) and a 47 month median survival (48% at 5 years). Moderate to severe complications were seen in 25% of patients, the most frequent complication being fibrosis of the breast or chest wall. There were two fatalities secondary to Adriamycin-induced cardiomyopathy. This study suggests better local control, with fewer complications, when surgery and irradiation are combined with multiagent chemotherapy. Further prospective clinical trials are strongly recommended.