The efficacy of "two-route chemotherapy (TRC)" using a combination of cisplatin (DDP) and its antidote, sodium thiosulfate (STS), was evaluated in rat bladder tumor. TRC in which 20 mg/kg of DDP and two doses of 1054 mg/kg of STS (100-fold molar ratio to DDP) were given during interruption of arterial flow for 30 minutes through the abdominal aorta and femoral vein, respectively, provided significantly better antitumor effects evaluated by tumor weight and survival time than did intra-arterial or iv DDP (4 mg/kg) without STS. These three modalities revealed a similar toxicity in rats. Dose- and time-related efficacy of DDP and a high sensitivity of a transitional cell carcinoma of the rat to DDP were noted in TRC. Nephrotoxicity assessed by increase in BUN levels was minimum. The particular combination of intra-arterial DDP and iv STS presented here is applicable to regionally confined human bladder cancer.