Twenty-eight patients with inflammatory carcinoma of the breast were managed initially by induction chemotherapy consisting of 3 courses of a combination of cyclophosphamide, doxorubicin hydrochloride, and 5-fluorouracil. Twenty-two showed a partial response, and 21 underwent mastectomies. Histopathologic examination of the surgical specimens revealed no residual tumor in 2 breasts, but all 21 patients had residual metastases in their axillary lymph nodes. Postoperatively, they received the same chemotherapy. The other six patients who failed to respond to induction chemotherapy received radical radiation therapy followed by a combination chemotherapy regimen that consisted of cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone. Any patient in whom chemotherapy failed during the follow-up period was treated by radiation therapy and/or a combination of mitomycin-C and vinblastine as necessary. At the time of diagnosis, 17 patients who had no evidence of distant metastasis, i.e., stage III B disease, had disease-free survival ranging from 5 to more than 84 months, with a median of 30 months, and an overall survival of 7 to more than 120 months with a median of 32 months. The 5-year survival rate was 18%. The other 11 patients who had distant metastases, i.e., stage IV disease, had an overall survival ranging from 4 to 14 months. The results of this approach of initial systemic chemotherapy followed by local-regional cytoreductive therapy, then systemic therapy, might suggest some survival benefits in patients with stage III disease.