Glucagon-like polypeptide 1 (GLP-1) may be a major enterogastrone, slowing gastric emptying when released by intestinal nutrients. In six conscious dogs, we studied the effects of GLP-1, on antropyloric motility, gastric emptying, and transpyloric flow after instillation of 500 ml of saline into the stomach. The meal was given and recordings were started 15 min after intravenous bolus and infusion of either saline or three different doses of GLP-1. Intravenous GLP-1 produced a dose-related retardation of gastric emptying associated with a decrease in the number and volume of flow pulses in comparison to saline. This change in transpyloric flow was associated with an inhibition of antropyloric pressure waves, a stimulation of isolated pyloric pressure waves, and an increase in basal pyloric tone induced by intravenous GLP-1 infusion. Our findings show that GLP-1 has a potent dose-dependent inhibitory effect on transpyloric flow and gastric emptying. This effect is temporally associated with inhibition of antral "pumping" and stimulation of pyloric "braking" mechanisms.