The results of this study show that lower esophageal sphincter contractions occur during phases 2 and 3 of the gastric interdigestive migratory motor complex in humans. In one series of studies, esophageal, gastric, and duodenal pressures were monitored overnight for 12 h in 7 healthy, fasting subjects. A second group of 10 volunteers was studied for 12 h on two consecutive nights. Periods of gastric contraction that reached a maximum frequency of about 3/min were shown to be part of the migratory motor complex cycle because they occurred immediately before phase 3 migratory motor complex activity in the duodenum. In all subjects, gastric interdigestive contractions were accompanied by lower esophageal sphincter contractions that maintained a pressure barrier between the stomach and esophageal body. During late phase 2 and phase 3 gastric migratory motor complex activity, the lower esophageal sphincter contractions were especially vigorous. Mean basal lower esophageal sphincter pressure varied significantly during the interdigestive cycle. Lower esophageal sphincter pressure values were maximal during phase 3 of gastric migratory motor complex activity and minimal values occurred during phase 1. No episodes of gastroesophageal reflux occurred as a result of increase of intragastric pressure caused by interdigestive gastric contractions.