The prognosis of patients with stage D bladder cancer is dismal. This report expands the results of our efforts to modify the clinical course of such patients by administration of doxorubicin hydrochloride sandwiched around pelvic radiation. Pathologic stage D bladder cancer was recognized in 19 patients by evaluation of tissue obtained by radical cystectomy and pelvic lymphadenectomy (8), pelvic lymph node dissection (5) or biopsies (3), ileal conduit and pelvic lymph node biopsy (1), or transurethral biopsy of the bladder and prostate (2). Treatment of these patients with doxorubicin hydrochloride before and after radiation was initiated 3 to 4 weeks postoperatively. The treatment regimen consisted of 1) 60 mg. per M.2 doxorubicin intravenously every 3 weeks for 3 cycles, 2) 5,000 rad external radiation to the entire pelvis in 5 to 6 weeks and 3) doxorubicin for 5 cycles. The observed survival rates were 37 per cent at 3 years and 28 per cent at 5 years. The median survival time was 16 months. Five patients had no evidence of disease 13 to 63 months postoperatively. One patient underwent salvage cystectomy for recurrent bladder carcinoma at 33 months and had no evidence of disease at 74 months. One patient was alive with recurrent disease at 13 months. Three patients who died did not complete the protocol owing to metastatic disease, 8 lived 6 to 52 months without recognized disease and died of metastases, and 1 died of a second primary. The extent of surgical excision was not associated significantly with survival. Of 8 patients treated with radical cystectomy 7 suffered a significant obstruction of the small bowel that required decompression or bypass surgery and all 7 recovered completely. These preliminary observations indicate encouraging results with a high but manageable morbidity for this regimen.