The current treatment of pancreatic cancer with resection and/or radiation is considered unsatisfactory because of a high incidence of failure and a moderate incidence of complications. A sizable number of these patients present with localized or regional disease. Regional high-dose chemotherapy, such as with isolated perfusion, may offer an alternative therapy with low treatment-related morbidity and mortality and better end results in this group of patients. In an effort to develop such a treatment modality, we evaluated the pharmacokinetics and toxicity of mitomycin C (MMC) during isolated perfusion of pancreas in a canine model. From this study, it appears that a dose of 0.25 mg MMC/kg body weight is most suitable for isolated perfusion of pancreas at 39 degrees C, maintaining flow rate and pressure within physiologic range. Isolated perfusion with a dose of 0.25 mg/kg body weight has very mild short- and long-term toxicities and markedly increases drug delivery to the pancreas, duodenum, and peripancreatic lymph nodes, making it the most suitable dose for possible clinical application.