Responses of either hepatic or celiac vagal afferents to intraportal hepatic vein administration of 2-mercaptoacetate (MA) were examined in rats maintained on either a high-fat or low-fat diet. Afferent activity in both hepatic and celiac vagal afferents significantly increased after administration of MA, but the magnitude of these increases did not differ as a function of either diet. Responses of hepatic vagal afferents were highly variable across individual rats, whereas those of celiac vagal afferents were remarkably consistent across individual rats. These data suggest that MA-induced enhanced feeding in rats given a fat-enriched diet does not depend on a stronger hepatic and/or celiac vagal afferent response than that of rats given a low-fat diet. © 2002 Lippincott Williams & Wilkins.