We evaluated the effects of radiotherapy (total dose 6,100 rads; 1,500 intraoperative and 4,600 external irradiation) on urothelial carcinomas in 16 patients. Tumor response and the histopathological changes were evaluated. All but one of the patients were men. Mean patient age was 58 years. The urothelial tumors were graded from I-III according to the histological features and degree of invasion. Two were classed as grade I, 6 grade II and 8 grade III. The post-irradiation cystectomy specimens revealed no tumor cells in 9 cases (56%); 2 grade II and 7 grade III tumors. All cystectomy specimens revealed histopathological changes following radiotherapy: edema and congestion (16 cases), squamous metaplasia (11 cases), multinucleated giant cells (7 cases), fibroblast proliferation (6 cases), dystrophic calcification (4 cases), macrophages with lipids (3 cases) and osseous formation (1 case). The mean patient follow-up was 18 months. Four patients died (3 from the tumor). Mean patient survival was 12 months. The foregoing findings indicate that radiotherapy appears to be more effective in destroying the more undifferentiated and deeper urothelial carcinoma.