Local regional chemotherapy has yet to be proven superior to other methods of drug administration. While current studies are underway to assess the value of intraperitoneal chemotherapy in patients with gastrointestinal (GI) malignancies, many factors affect the success of such trials. Route of delivery and drug metabolism are all important. It is theorized that local exposure of liver with high concentrations of drug (even considering the limited efficacy of available agents) will result in improved tumor kill. In GI tumors, the putative route of spread is through the portal system to the liver. Intraperitoneal (IP) administration of drug offers an opportunity to deliver high concentrations of drug to local intraperitoneal surfaces, and, if there is sufficient hepatic extraction, IP administration also delivers a high concentration of drug to the liver. In a study of 5-fluorouracil (5-FU) in patients with metastatic colorectal carcinomas, high portal drug concentrations were achieved by this method of administration. It was concluded that IP therapy is an excellent method of delivering high concentrations of 5-FU and possibly other drugs to the hepatic parenchyma as well as to the intraperitoneal space. Since the effectiveness of such administration of still unclear, further clinical trials are indicated.