In an attempt to improve the poor prognosis of invasive and/or high-grade bladder cancer after total cystectomy, we tried a combination of regional irradiation with hyperthermia (RH) therapy and systemic M-VAC (methotrexate, vinblastine, Adriamycin, and cisplatin) chemotherapy followed by surgery. The short-term results of these treatments were evaluated. A total of 17 patients received the combination of RH and M-VAC therapy between January 1989 and July 1990, and 12 then underwent total cystectomy. Of the 17 patients, 14 were evaluable for tumor response. The objective response rate was 64% (9/14), with 4 patients achieving a complete remission that was confirmed by histological examination. Nausea and vomiting were inevitable, and 71% (12/17) of the patients developed leukopenia. However, these side effects were not serious. Considering the previous results obtained using RH therapy in the absence of chemotherapy for this disease, no significant difference in the tumor response was detected between the RH only group and the RH plus M-VAC group. The long-term results cannot yet be evaluated, but we will continue to follow these patients in the future so as to clarify the usefulness of M-VAC therapy as preoperative therapy.