The surgically created squamocolumnar junction in patients who have undergone an esophagogastrostomy after partial esophagogastrectomy provides a unique opportunity to study mucosal regeneration in the setting of gastroesophageal reflux. The pathological and clinical findings in 17 such patients are presented. In each patient the anastomosis had been performed between histologically documented squamous-lined esophagus and gastric fundus. Cardiac type mucosa had regenerated in the region of the anastomosis in 9 patients and was detected as early as 2 months after operation. In addition, 3 patients, 2 of whom had cardiac type mucosa, had acquired Barrett or Barrett-like mucosa on the distal esophagus by 76 to 119 months. Gastroesophageal reflux was prominent in all 3 of these patients. The findings strongly support the hypothesis that the distinctive mucosa of Barrett's esophagus develops after reflux-induced ulceration and subsequent mucosal regeneration by immature cells that are derived from cardiac and/or fundic mucosa, and which undergo specialized differentiation in the presence of reflux.