Manometric measurements of the lower esophageal sphincter have shown that a decrease in resting pressures is the major factor in the pathogenesis of gastroesophageal reflux. About one-fourth of patients with reflux esophagitis, however, have LES pressures that overlap with those of controls, suggesting that other factors may also contribute to the development of reflux esophagitis. Among the additional factors that have been postulated as important are the esophageal acid clearance, the resistance of the esophageal squamous epithelium, the concentration of the causative agents (hydrochloric acid, pepsin, and bile salts), and perhaps the rates of gastric emptying. Nevertheless, in addition to the manometric data, there is a large body of evidence based on clinical, pathological, pharmacological, and therapeutic studies that strongly supports the concept that the lower esophageal tone is the required condition for all other secondary factors to play a role in the pathogenesis of reflux esophagitis.