Esophageal acid clearance normally occurs as a two-step process. The initial step of emptying most of the fluid volume contained within the esophagus occurs quickly by gravity or by one or two peristaltic sequences. However, volume clearance is distinct from acid clearance, and esophageal pH is restored to normal after volume clearance as the 1 mL or so of residual acid is neutralized by swallowed saliva in a stepwise fashion. A considerable body of evidence has accumulated suggesting that about half of patients with reflux disease have markedly prolonged acid clearance times. Within this group abnormalities or both volume clearance and salivation have been demonstrated. Volume clearance may be impaired as a result of a breakdown of the peristaltic mechanism commonly seen with severe esophagitis or by "re-reflux" of cleared fluid from within a hiatal hernia. Either way, the result is increased residual acidic fluid within the esophagus. The increased residual acid must be titrated with saliva that has so slight a neutralizing capacity that it takes about 7 minutes for the average person to secrete enough saliva to titrate 1 mL of 0.1 N HCl. Salivation itself is reduced in cigarette smokers and in patients using anticholinergic medications, thereby prolonging the process of mucosal neutralization in such persons. Whatever the mechanism of prolonged acid clearance for a particular individual, the overall result is of prolonged esophageal mucosal acid exposure, which makes the development of peptic esophagitis more likely.