Single and combination chemotherapy was evaluated for antitumor activity against N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT)-induced bladder carcinoma in syngeneic mice. Two hundred fifty C3H/He mice having ingested FANFT for 10 months were randomly divided into groups of 30, and the following regimens initiated: cyclophosphamide (Cy), cis-diam-minedichloroplatinum (cis-Pt-II), dactinomycin, adriamycin, Cy plus cis-Pt-II, Cy plus 5-fluorouracil, and Cy plus adriamycin. The drugs were administered for 3 weeks. Each regimen was capable of producing a significant reduction in the mean bladder weight (MBW) when compared to a groups not receiving therapy (108.3 mg). Adriamycin (MBW equal 69.5), dactinomycin (49.6), and cyclophosphamide (42.9) were the best single agents, but the greatest inhibition of tumor growth was achieved by the combination of cyclophosphamide with 5-fluorouracil (38.3) or adriamycin (37.3). These combination chemotherapeutic regimens were able to effect a significant reduction in the number of bladders with Stage C tumors. It is hoped that information gained from this new animal model which allows evaluation of many antitumor drugs within a relatively short period of time will lead to therapeutic trials in patients with locally advanced or metastatic bladder cancer.