In this study, we evaluated factors that affect esophageal acid clearance in normal subjects. A 15-ml bolus of 0.1 N HCl (pH 1.2) was injected into the esophagus, and the subject then swallowed every 30 s. Manometric and pH monitoring demonstrated that esophageal acid clearance occurred by a series of step increases in pH, each associated with a swallow-induced peristaltic sequence. Between peristaltic sequences, pH increase was minimal. Saliva stimulation by oral lozenge greatly improved acid clearance, while oral aspiration of saliva abolished the step increases in esophageal pH and markedly delayed acid clearance. Replacement of aspirated saliva with a bicarbonate solution reproduced the step increases in esophageal pH and restored acid clearance toward normal, while replacement with water alone failed to improve acid clearance. Similar to the effect of the oral lozenge, bethanechol (5 mg subcutaneously) improved esophageal acid clearance, but this improvement was reversed by oral aspiration of saliva, which markedly delayed acid clearance. A change from the recumbent to the sitting position tended to improve acid clearance slightly, but this improvement was not statistically significant. We concluded that in normal subjects (a) swallowing carries saliva into the esophagus and peristalsis empties intraesophageal fluid into the stomach, (b) the neutralization of acid by saliva carried into the esophagus with each swallow accounts for the occurrence of acid clearance by step increases in pH, (c) the improvement in acid clearance with bethanechol is due to saliva stimulation, and (d) gravity contributes little to esophageal acid clearance in the presence of normal peristaltic stripping waves.