Our purposes were to: (1) develop an animal model where iv administered D-glucose consistently inhibited antral motility, and (2) use this model (a) to assess whether iv glucose acts to inhibit motility from a peripheral or a CNS site, and (b) to elucidate the factor(s) that determine(s) whether stomach motor function is sensitive to changes in blood glucose. Rats were anesthetized with -chloralose/urethane, and antral motility was measured by a strain gauge force transducer sutured to the antrum; in some cases, antral motility and gastric tone were measured by monitoring intragastric balloon pressure. Increases in blood glucose were produced by continuous iv infusion of 25% D-glucose at 2 ml/hr. Inhibition of antral motility and gastric tone were observed when gastric contractions were induced by hypoglycemia (subcutaneously administered insulin, 2.5 IU/animal). In contrast, no inhibition of gastric motor function was observed when glucose infusion was tested on gastric contractions that were: (a) spontaneously-occurring, (b) evoked by iv administered bethanechol in vagotomized animals, and (c) evoked by the TRH analogue, RX77368, microinjected into the dorsal motor nucleus of the vagus. Using the model of insulin-induced hypoglycemia to increase gastric motor activity, we found that neither sectioning the hepatic branch of the vagus (n=5), nor treating animals with capsaicin to destroy sensory vagal afferent nerves (n=5), affected the ability of iv D-glucose to inhibit gastric motor function. Our results indicate that an important factor determining whether stomach motor function will be sensitive to changes in blood glucose is the method used to stimulate gastric contractions, and that the primary site of the inhibitory action of iv glucose on gastric motility is the CNS rather than the periphery.