Barrett's esophagus is a common finding in patients with gastroesophageal reflux and is associated with a high incidence of serious complications (stricture, ulceration, and carcinoma). The reason that only a portion of patients with reflux develop Barrett's esophagus and why some are prone to develop complications is unknown. Twenty-three patients with Barrett's esophagus underwent endoscopy, 24-hour esophageal pH monitoring, and manometry. Nine of these patients with gastritis underwent 24-hour gastric pH monitoring, and three with symptoms of duodenogastric reflux underwent 99mTc-labeled hepato-iminodiacetic acid scanning. Patients with complicated (n = 12) and uncomplicated (n = 11) Barrett's esophagus were compared with each other and with patients with reflux esophagitis (n = 53) and normal volunteers (n = 50). Patients with Barrett's esophagus showed an increased exposure to acid and alkaline gastric juice compared with patients with esophagitis and normal volunteers. In the patients with Barrett's esophagus with and without complications, there was no significant difference in age, incidence of defective lower esophageal sphincter, incidence of defective peristalsis, extent of the Barrett's epithelium, or percent time the esophageal pH was less than 4. In contrast, the percent time the esophageal pH was greater than 7 was significantly greater in patients with complications. This alkaline exposure is likely to be related to duodenogastric reflux. This was supported by positive gastric pH scores for duodenogastric reflux and 99mTc-labeled hepato-iminodiacetic acid scans in patients with Barrett's complications. These findings suggest that the development of complications in Barrett's esophagus is the result of the damaging effect of refluxed duodenal juice.