Two experimental methods for use in kinetic studies on a compartment model for intestinal metabolism and absorption were evaluated. The in vitro cannulated everted intestinal sac and the in vivo intestinal loop with complete mesenteric venous collection were compared in the same region of rabbit intestine. These experimental methods were used to study the effects of metabolism, tissue accumulation, and blood flow on the transport of sali-cylamide across the basal barrier and provide experimental evidence to support the cell compartment model. At lower initial mucosal concentration (10−3M), over 60% of the drug appearing in mesenteric blood is conjugated with glucuronic acid. At higher initial mucosal fluid concentrations, glucuronide conjugation appears to be capacity limited and the disappearance from the lumen-curve shows a distinct distributive phase characteristic of a cell compartment model. The rate of transport of free drug across the basal barrier is blood flow rate-limited while the transport of glucuronide is essentially independent of blood flow. Appearance of free salicyl-amide into mesenteric blood, in vivo, shows a lag time of 4 min. compared to a lag time of about 10 min. for the appearance of free drug into serosal fluid in vitro. The steady state rate of appearance of free drug into the plasma (in vivo) is five to ten times greater than the rate of appearance of free drug into the serosal fluid (in vitro) at similar mucosal concentrations. The in vivo intestinal loop with complete venous collection was found to have many advantages in studying physiological factors of intestinal drug absorption.