Nine patients with locally advanced transitional cell carcinoma (TCC) of the bladder were treated with neoadjuvant methotrexate, vinblastine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (M-VAC) followed by radical cystoprostatectomy and modified pelvic lymphadenectomy. Five patients, including three with pelvic sidewall fixation, had clinical stage T4N0M0 tumors whereas the remaining patients had T3N0M0 tumors. All patients were pathologically restaged by a referee pathologist after surgery. The complete response rate was 22% and an additional 44% experienced a partial response. Neutropenia preventing a second cycle of M-VAC occurred in one patient. Downstaging of locally advanced TCC of the bladder was achieved in the majority of patients treated with neoadjuvant M-VAC.