Pharmacokinetic comparison of 5-Fluorouracil (5-Fu) administered ip versus iv was made in rabbits. Ip administration of bolus and large volume of 5-Fu could maintain high, stable and sustained concentration in the peritoneal cavity, portal vain and liver while sparing the systemic circulation. After iv bolus administration of 5-Fu, drug concentration in the systemic circulation was very high. Although iv administration of 5-Fu could lead to high concentration in the portal vein and liver, sustainment of concentration was relatively of short duration and the 5-Fu concentration was very low in the peritoneal fluid. The authors believe that ip chemotherapy has a significant pharmacokinetic advantage over the conventional iv route in preventing and treating recurrences in the peritoneal cavity and liver metastasis after surgery for gastro-intestinal malignancies.