The aim of this study was to investigate the hypothesis that during the postprandial period in humans, dopamine interrupts the gastrointestinal motility pattern through a mechanism that is peptide-mediated. Fourteen normal human subjects were studied by means of intestinal manometry. After recording two consecutive migrating motor complexes a 900-kcal solid-liquid meal was given. In eight subjects 30 min after the meal, placebo or dopamine (5 micrograms/kg/min) was infused for 15 min and then the recording continued for 120 min. In the remaining six subjects dopamine was administered twice with a 90-min interval in between. In three subjects the first dopamine infusion after the meal was preceded by treatment with placebo, the second by domperidone (20 mg intravenous as bolus), in the other three subjects domperidone was given before the first dopamine infusion. Blood samples for the determination of somatostatin and motilin were drawn basally, during, and immediately after dopamine in seven subjects. The results show that dopamine interrupts the fed motility pattern, inhibiting the high antral waves, and activates a duodenal phase III of migrating motor complexes. The pretreatment with domperidone completely prevented the dopamine effect. Plasma levels of motilin increased significantly during dopamine, while somatostatin blood levels did not change. These findings support the hypothesis that a dopaminergic mechanism may modulate the cycling of duodenal motor complex in humans.