Summary Duodenal ulcers were produced in fasted rats by constant subcutaneous infusion of histamine dihydrochloride (0.1 mg/kg/min) plus carbachol (0.3 μg/kg/min), two potent gastric secretogogues. These ulcers were perforated in many animals, and 36% of those so treated died of peritonitis. When the animals were given food and water during infusion of the secretogogues, none died nor had duodenal perforations, and only a few showed duodenal ulcers, which were mild. These results are reminiscent of the beneficial effect of feeding on ulcer symptoms in man. Duodenal ulcers produced by the secretogogues used in this study are probably due to excessive secretion of gastric juice, and it is likely that the protection afforded by food results from the buffering of this strongly acid and peptic gastric juice.