Oleoylethanolamide (OEA) may be an endogenous regulator of food intake, and intraperitoneal injection of this compound decreases food intake in 24 h-starved rats. It is generally believed that this kind of lipid amide is rapidly catabolized in the gastrointestinal tract, thereby preventing its use as an oral antiobesity compound. We now show that oral OEA inhibits food intake dose dependently at 90 min after food presentation to starved rats. Food intake was reduced by 15.5% (P < 0.01) by administration of 10 mg/kg OEA. [(3)H]OEA was used to assess the degree of catabolism in the gastrointestinal tract. The endogenous level of this acylethanolamide was increased 11 times in the intestinal tissue (to 3.91 +/- 0.98 nmol/g tissue, mean +/- SEM) at 90 min after food presentation, based on the finding of 0.48% of the dose as intact OEA. These findings reveal unexpected properties of orally administered OEA, which may have potential as a cheap and safe antiobesity drug.