As neoadjuvant chemotherapy for advanced bladder cancer, the intra-arterial administration of methotrexate (MTX), Adriamycin (ADM), and cisplatin (CDDP; IA-MAC) was evaluated. A total of 48 patients with bladder cancer (greater than or equal to T2 or CIS) were selected and received 30.1 mg MTX, 34.5 mg ADM, and 89.1 mg CDDP as an average course. The mean tumor-regression rate after 2 or 3 weeks was 52.3%, and patients with grade 3 transitional-cell carcinoma showed the best results, achieving a 69.6% regression rate. In 30 cases (63%), downstaging was observed. Among the 46 patients who underwent subsequent surgical therapy, the bladder could be preserved in 26 cases by transurethral resection or segmental resection. According to the criteria of the Japanese Association of Cancer Therapy, a histological effect of GIII or better was obtained in 15 cases (29%). The histological effect correlated well with the tumor-regression rate. As compared with intravenous therapy with MTX, vinblastine, ADM, and CDDP (M-VAC), IA-MAC treatment was well tolerated due to its lower degree of bone marrow suppression, and it resulted in a longer disease-free interval and better survival. In addition, the period prior to surgical therapy was shortened in this study. These results suggest that IA-MAC chemotherapy can be useful as an arm of multidisciplinary treatment of advanced bladder tumors.