This study determines the relationship among esophageal dysmotility, esophageal acid exposure, and esophageal mucosal injury in patients with gastroesophageal reflux disease (GERD). A total of 827 patients with GERD (confirmed by ambulatory pH monitoring) were divided into three groups based on the degree of mucosal injury: group A, no esophagitis, 493 patients; group B, esophagitis grades I to III, 273 patients; and group C, Barrett's esophagus, 61 patients. As mucosal damage progressed from no esophagitis to Barrett's esophagus, there was a significant decrease in lower esophageal sphincter pressure and amplitude of peristalsis in the distal esophagus, with a subsequent increase in the number of reflux episodes in 24 hours, the number of reflux episodes longer than 5 minutes, and the reflux score. These data suggest that in patients with GERD, worsening of esophageal mucosal injury may determine progressive deterioration of esophageal motor function with impairment of acid clearance and increase of esophageal acid exposure. These findings suggest that Barrett's esophagus is an end-stage form of gastroesophageal reflux, and that if surgical therapy is performed early in the course of the disease, this cascade of events might be blocked.