Surgical procedures for the chronic cannulation of the portal and the femoral veins in the rat are described. The surgical procedure for portal vein cannulation is delicate and requires practice, but has proven useful for chronic drug administration. Cannulation of the femoral vein was less involved and cannula patency was extended by proper cannula preparation and placement. This dual cannulation of the rat allowed infusion of racemic mephenytoin into the portal vein and blood collection from the femoral vein for characterizing blood concentrations of the individual isomers. Chronic portal vein drug infusions may provide a useful approach to studies of time-dependent change in hepatic metabolism and stereoselective first-pass drug elimination in unrestrained animals.