To study the influence of reflux esophagitis on the carcinogenic response of 2,6-dimethylnitrosomorpholine (2,6-DMNM), an experiment was designed, composed of 6 groups of 8-week-old Sprague-Dawley rats, each consisting of 20 males and 20 females. Group 1 served as untreated controls. All animals of groups 2, 4, and 6 underwent an esophagojejunostomy with gastric preservation to produce a chronic reflux esophagitis. 2,6-DMNM was injected s.c. once weekly for life at doses of 1/100 and 1/10 of the 50% lethal dose to groups 3 and 4 and groups 5 and 6, respectively. Carcinogen exposure began in groups 4 and 6 15 days after the esophagojejunostomy. Squamous cell carcinomas were observed in the esophagus of 36 animals, mainly in those receiving the higher dose. Exophytic squamous cell carcinomas, a variety rarely seen in humans, were mostly seen in the groups receiving 2,6-DMNM alone, whereas endophytic squamous cell carcinomas, the variety most frequently seen in humans, mainly developed in the groups receiving the combined treatment. In addition adenocarcinomas with abundant mucin production were found in the distal esophagus of 23 animals. They were found exclusively in animals of groups 4 and 6 which underwent esophagojejunostomy plus 2,6-DMNM exposure. No adenocarcinomas were encountered in groups without experimental reflux esophagitis. These findings may contribute to further understanding of the association between reflux esophagitis and the various histological types of esophageal carcinoma in humans.