Glucagon-like peptide (GLP)-1 inhibits acid secretion and gastric emptying in humans, but the effect on acid secretion is lost after vagotomy. To elucidate the mechanism involved, we studied its effect on vagally stimulated gastropancreatic secretion and motility in urethan-anesthetized pigs with cut splanchnic nerves, in which insulin-induced hypoglycemia elicited a marked stimulation of gastropancreatic secretion and antral motility. In addition, we studied vagally stimulated motility and pancreatic secretion in isolated perfused preparations of the porcine antrum and pancreas. GLP-1 infusion (2 pmol. kg-1. min-1) strongly and significantly inhibited hypoglycemia-induced antral motility, gastric acid secretion, pancreatic bicarbonate and protein secretion, and pancreatic polypeptide (PP) secretion. GLP-1 (at 10(-10)-10(-8) mol/l) did not inhibit vagally induced antral motility, pancreatic exocrine secretion, or gastrin and PP secretion in isolated perfused antrum and pancreas. We conclude that the inhibitory effect of peripheral GLP-1 on upper gastrointestinal secretion and motility is exerted via interaction with centers in the brain or afferent neural pathways relaying to the vagal motor nuclei.