Resveratrol, which is present in grapes, wine and peanuts, is believed to possess chemoprotective properties such as anticarcinogenic effects and to provide protection against cardiovascular diseases. Little is known, however, about its intestinal absorption. We investigated the absorption and metabolism of resveratrol by using an isolated preparation of luminally and vascularly perfused rat small intestine. A synthetic perfusate free from blood components was used as vascular medium with a perfluorocarbon as oxygen carrier. Luminal media consisted of a bicarbonate buffered sodium chloride solution spiked with resveratrol in physiological, nutritionally relevant concentrations (28, 34 and 57 micromol/l, respectively). Viability was maintained during the entire perfusion and no significant differences between resveratrol and control perfusions for oxygen consumption, arterial pressure, lactate-pyruvate ratio and acid-base homeostasis were observed. Vascular uptake of luminally administered resveratrol was 20.5%. The majority of the absorbed resveratrol was conjugated to yield resveratrol glucuronide (16.8%), which was also the main luminal metabolite (11.2%). Lesser amounts of resveratrol sulfate, 3.0% and 0.3%, were found on the luminal and vascular side, respectively, while only minute amounts of resveratrol and resveratrol conjugates (1.9%) were found in the intestinal tissue. The structures of the resveratrol conjugates were verified by liquid chromatography coupled with mass spectometry (LC-MS). The results demonstrate an ample uptake and metabolic conversion of resveratrol. The proposed perfusion model serves as a tool to evaluate intestinal absorption and metabolic handling of phytochemicals, a pertinent input to the ongoing discussion about their health benefits.