To test the hypothesis that vagally mediated metabolic signals from the liver affect feeding, we investigated the influence of selective hepatic vagotomy on the anorectic effect of different metabolites in rats. Subcutaneous injection of glycerol (GLY), D-3 hydroxybutyrate (DHB), L-malate (MAL), L-lactate (LAC), or pyruvate (PYR) (5.7 mmol/kg metabolic body weight = b.wt.0.75, each) reduced food intake in sham-vagotomized rats. Selective hepatic vagotomy eliminated the hypophagic effect of all metabolites. In an additional experiment, LAC retained its potency to inhibit feeding in sham-vagotomized rats after an intraperitoneal injection of atropine methylnitrate (5 mg/kg b.wt.0.75). The results demonstrate that the hypophagic effect of GLY, DHB, MAL, LAC and PYR originates in the liver and is mediated by hepatic vagal afferents. This implicates the existence of adequate hepatic receptors which might contribute to the control of food intake.