It is now accepted that the incidence of esophageal carcinoma is highest in the middle thoracic region. Esophageal carcinoma after gastrectomy, however, has a tendency to develop in the lower region. This study was designed to investigate the role of reflux of gastroduodenal juice in the genesis of carcinoma in the esophagus. We found a possible correlation between the development of esophageal carcinoma and gastrectomy, related to alkaline reflux into the esophagus. To elucidate this correlation, the role of alkaline reflux of duodenal contents in the development of esophageal squamous cell carcinoma was investigated in Wister rats. Gastrectomized rats with regurgitation of duodenal contents into the esophagus were not administered any carcinogen and were sacrificed some at the end of 8 weeks and others at 50 weeks for pathological examination. Hyperplasia was found in rats at 8 weeks, and the esophageal squamous cell carcinoma was found in rats at 50 weeks. The carcinomas were found exclusively in the area of the reflux esophagitis and were accompanied by severe dysplasia. These results suggested that alkaline reflux of duodenal contents was strongly correlated to the development of the esophageal squamous cell carcinoma.