The therapeutic efficacy of "two-route chemotherapy" (TRC) using cisplatin (DDP) and its potent antidote, sodium thiosulfate (STS), was studied on rat metastatic liver tumors. Twenty mg/kg of DDP was given to rats via the hepatic artery in combination with systemic STS at a dose of 1054 mg/kg (100-fold molar ratio to 20 mg/kg of DDP) or at two doses of 1054 mg/kg. As controls, 5 or 4 mg/kg of DDP alone was given intra-arterially or iv. Antitumor effects were evaluated by prolongation in lifespan after the tumor cell inoculation. Side effects were assessed by weight loss, BUN, and serum transaminases after the chemotherapy. TRC resulted in the longest lifespan, with a minimum weight loss and without elevation of BUN or serum transaminases. The therapeutic efficacy of TRC was enhanced by temporary ligation of the portal vein for 5 minutes, performed simultaneously with DDP infusion. Our findings clearly indicate the effectiveness of TRC using intra-arterial DDP in a high dose and in combination with iv STS.