Because the absorption of orally administered drugs depends on intestinal permeability, we have investigated how absorptive capacity varies from the proximal to distal intestine in rats. The effective permeabilities of compounds with a range of physicochemical properties and different absorption mechanisms were estimated by use of a previously validated in-situ, single-pass perfusion model. The low colonic permeabilities of D-glucose and L-dopa indicate the absence or low capacity of the glucose- and amino-acid-transporters in this region. With the exception of the small and moderately lipophilic non-steroidal anti-inflammatory drug, naproxen, for which permeability was maintained throughout the intestine, the passive intestinal permeabilities for hydrophilic and lipophilic drugs were approximately twice as high in the jejunum and ileum as in the colon. These observations are in accord with those made in recent studies. However, the reasons for the high colonic permeability of non-steroidal anti-inflammatory drugs, and results obtained in previous animal experiments demonstrating that the colon is the region of the intestine with the highest absorptive capacity were not fully clarified. These data show that the permeability to hydrophilic and lipophilic drugs decreases along the intestine, whereas it is maintained throughout the intestine for the small and moderately lipophilic naproxen. Further investigations are required to clarify the interplay between membrane composition, fluidity and permeability under various conditions in different absorption models.