Male Wistar rats were subjected to one of three types of operative reflux procedure that allowed part or all of the duodenal contents to flow back into the stomach through the pylorus, thus producing models of bile reflux alone, pancreaticoduodenal reflux alone, and combined reflux. All surviving animals were killed 50 weeks after surgery and the development of gastric cancer was assessed. No cancer was seen in 16 animals with pancreaticoduodenal reflux or in 32 control animals with gastrotomy, whereas 2/8 animals with bile reflux and 11/29 animals with combined reflux had gastric carcinoma. Compared with the control group, the incidence of carcinoma in animals with bile or combined reflux was significantly higher (P less than 0.05 and P less than 0.01 respectively). All carcinomas developed in the antral area near the pylorus. Adenomas were observed only in the groups of animals developing carcinoma and occurred in the same region of the stomach. These results suggest that bile, and not pancreaticoduodenal secretions, is the component of the duodenal contents responsible for the development of gastric carcinoma.