Epidemiological studies have shown that the incidence of heart disease and certain cancers is lower in the Mediterranean region. This has been attributed to the high consumption of olive oil in the Mediterranean diet, which contains polyphenolic compounds with antioxidant activity. Although many in vitro studies have been performed to elucidate mechanisms by which these compounds may act, there are virtually no data relating to their fate after ingestion. Therefore, we decided to investigate the intestinal absorption of one of the major olive oil polyphenolics, oleuropein. To do this, a novel in situ intestinal perfusion technique was developed, and the absorption of oleuropein was studied under both iso-osmotic and hypotonic luminal conditions. Oleuropein was absorbed, with an apparent permeability coefficient (P:(app)) of 1.47 +/- 0.13 x 10(-6) cm/s (+/-SE) observed under iso-osmotic conditions. The mechanism of absorption is unclear but may involve transcellular transport (SGLT1) or paracellular movement. Under hypotonic conditions, the permeability of oleuropein was significantly greater (5.92 +/- 0.49 x 10(-6) cm/s, P: < 0.001). This increase is thought to be due to an increase in paracellular movement facilitated by the opening of paracellular junctions in response to hypotonicity. Overall, we determined that the olive oil polyphenolic oleuropein can be absorbed, albeit poorly, from isolated perfused rat intestine. Therefore, it is possible that it or its metabolites may confer a positive health benefit after the consumption of olive oil, most likely via an antioxidant mechanism.