There has been increasing interest in the potential use of erythromycin as a prokinetic agent, despite limited data on the effect of oral administration on gastrointestinal motility. We have now evaluated, in 15 conscious pigs fitted with strain gauges, the response of (i) basal gastric motility and (ii) gastric motility during inhibition with intraduodenal triglycerides infusion to increasing doses of oral erythromycin. In the basal state, erythromycin led to dose-dependent increases in both the amplitude (10-30 mg kg-1) and the frequency (10-55 mg kg-1) of gastric contractions. The corpus was more responsive than the antrum, with an increase in amplitude at lower doses. The amplitude of the duodenal contractions was also improved but not in a dose-dependent manner. Gastroduodenal coordination was unchanged regardless of the dose of erythromycin. Following inhibition of gastric motility, a dose of erythromycin below 45 mg kg-1 increased both the amplitude of gastric contractions and the gastroduodenal coordination, although individual doses produced smaller increases in amplitude than in the basal state. These results suggest that erythromycin has a different mechanism of action in the stomach compared with the duodenum. The reduced effectiveness of large doses of erythromycin has important therapeutic implications.