BACKGROUND: Glucagon-like peptide 1 (GLP-1) is an intestinal hormone that is secreted in response to meal ingestion. GLP-1 inhibits gastric emptying and reduces postprandial gastric secretion and may play a physiological regulatory role in controlling appetite and energy intake in humans. The GLP-1 receptors have been identified in several organs including the stomach, brain and pancreas. The GLP-1 mechanism of action on insulin secretion is at least partly mediated via receptors on the pancreatic islet, but the mechanism by which GLP-1 retards gastric emptying is not known and may involve neural interactions, although GLP-1 has no effect on vagally stimulated motor activity of the isolated porcine antrum. MATERIAL AND METHODS: Previously, an experimental model was developed with centrally (insulin hypoglycaemia) induced vagally mediated stimulation of antral motility, recorded by force transducers, in anaesthetized pigs. This model has now been developed further to include vagal deafferentation to determine the role of the afferent vagus in mediating the inhibitory effect of GLP-1 on gastric motility. RESULTS: Intravenous infusion of GLP-1 resulting in slightly supraphysiological plasma levels inhibited the antral contractile force, with the amplitude falling from 29.9+/-5.7 mm to 14.6+/-3.5 mm (p<0.001). After vagal deafferentation GLP-1 still inhibited antral motility (from 36.6+/-6.4 mm to 25+/-4.4 mm (p<0.019). The decrease in amplitude was the same before and after deafferentation. CONCLUSIONS: GLP-1 significantly inhibited centrally induced antral motility and the inhibitory effect of GLP-1 on gastric motility persisted after vagal deafferentation, supporting the hypothesis that the inhibitory effect results from direct interaction of GLP with receptors in the CNS, which in turn reduce vagal efferent output.