Cisplatin (DDP) is attractive for use in regional chemotherapy because of its tendency for protein binding. A study of regional chemotherapy was conducted in rabbits bearing the VX-2 carcinoma. Modes of therapy examined were intravenous (IV), intra-arterial (IA), IA with stopflow, IA with outflow occlusion, and isolation-perfusion (I-P). Each mode was evaluated by examining the pharmacokinetics of DDP in systemic and regional administration and measuring tissue concentrations of DDP. It was observed that the systemic exposure to DDP was significantly less for IA with outflow occlusion and I-P when compared to IV, IA, or IA with stopflow occlusion (P = 0.003). Tumor concentrations were highest with IA infusion with outflow occlusion (P = 0.002) and IA stopflow occlusion (P = 0.03). Tumor tissue concentrations were always higher than adjacent muscle DDP concentrations. The authors conclude that significant pharmacologic advantage can be demonstrated for certain modes of DDP administration in this rabbit model, and that these promising results should be followed by clinical trials.