As clarithromycin (CLA), an antibiotic commonly used for Helicobacter pylori eradication, stimulates gastroduodenal motility, we investigated whether it also stimulates esophageal motility. In 15 normal subjects, esophageal motility was recorded using a low-compliance manometric system with two ports in the esophageal body, one port in the lower esophageal sphincter (LES), and five ports in the antroduodenal tract to monitor the occurrence of phases I-III of the migrating motor complex. Thirty minutes after the occurrence of a duodenal phase III, we infused intravenously, randomly, and in a double-blind manner, CLA 100 mg in five subjects (group A), CLA 250 mg in five subjects (group B), and normal saline in the remaining five subjects (group C). LES tone and post-deglutitive residual pressure, as well as the amplitude and duration of the esophageal contractions, were measured each minute and averaged over a post-infusion period of 30 min. Both group A and B showed a LES tone significantly higher than that of group C after CLA infusion, whereas the post-deglutitive residual pressure was not significantly different from that of group C. The LES tone of group B was significantly higher than that of group A. Group B, but not group A, showed a wave amplitude and duration significantly higher than that of group C. In conclusion, CLA is able to stimulate LES tone and esophageal contractions with a dose-related effect.