The gastrointestinal absorption characteristics of pafenolol following oral administration as a solution in man and rat has previously been found to be a double-peak phenomenon and exhibited dose-dependent bioavailability, despite negligible presystemic metabolism. In both man and rat the first peak appeared approximately 0.5-1 hr postdose and the second, more pronounced peak 3-4 hr postdose. In rat more than 90% of the available dose was absorbed during the second peak. In the present study we investigated the absorption of a solution of pafenolol in rats after intrajejunal and intraileal administration. The resulting blood concentration-time profile of pafenolol exhibited one peak only; the extent of absorption was similar to that observed when the same dose was given orally. The small intestinal transit time of the 14C-PEG 4000 solution was found to be more than 3 hr. The transit rate was higher in the proximal part of the small intestine compared to the more distal part, where the transit of the solution was staggered. In conclusion, the results of the intestinal transit time investigation and the administrations of pafenolol at different levels of the alimentary tract indicate that pafenolol is a drug with a specific absorption site located in the ileocolonic region.