Motilin induces phase III activity of the gastrointestinal tract. Erythromycin has a motilin-like effect on the stomach and significantly increases the lower esophageal sphincter (LES) pressure in normal volunteers. This investigation was performed to evaluate the effects of erythromycin on esophageal function in patients with gastroesophageal reflux disease (GERD). Esophageal manometry was performed in 10 GERD patients before and after intravenous infusion of 500 mg of erythromycin. Values are expressed as mean +/- SEM. LES pressure increased from 13.9 +/- 2.9 mm Hg at baseline to 28.9 +/- 3.6 mm Hg after infusion of erythromycin (p < 0.01). The duration of contractions in the proximal, middle, and distal esophagus was significantly prolonged from 3.5 +/- 0.4 seconds, 3.8 +/- 0.4 seconds, and 4.1 +/- 0.5 seconds to 4.2 +/- 0.2 seconds, 4.6 +/- 0.5 seconds, and 5.6 +/- 0.6 seconds, respectively, after infusion of erythromycin (p < 0.05 for each comparison). Erythromycin did not effect esophageal body contraction amplitude or velocity, or the upper esophageal sphincter. Serum motilin decreased slightly after the administration of erythromycin. We concluded the following: (1) Erythromycin profoundly stimulates the defective LES in patients with GERD. This appears to be a direct motilin agonist-like effect rather than being mediated by release of endogenous motilin. (2) Erythromycin has less effect on the esophageal body, although it does prolong the duration of esophageal contractions.