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We have shown previously that supplemental vitamin A (Vit. A) increases the early inflammatory response to wounding and enhances the collagen content of the intestine of normal and injured rats. We now report the effect of dietary supplementation with Vit. A on the prevention of duodenal ulcer (DU) in rats caused by intragastric administration of cysteamine-HCl. A major way cysteamine-HCl induces DU formation is by enhancing gastric acid secretion. Adult male rats were divided into two groups: (1) rats fed a standard rat Chow (Purina) (15 IU Vit. A/g diet) containing two to three times the National Research Council recommended daily allowance for Vit. A for normal rats; (2) rats fed the same supplemented with 150 IU of Vit. A palmitate per/g Chow. One week later, all rats were given 1 ml of cysteamine-HCl (135 mg) intragastrically. The rats were maintained on their respective diets. Two days later, all rats were killed with ether, the stomach and duodenum excised, and examined for the presence of ulcers. No gastric ulcers were found in either group. There was a statistically significant decrease in the incidence of DUs in the Vit. A-supplemented group when compared to the control group (p less than 0.01) 48 hr following cysteamine-HCl administration; 32% of the Vit. A-supplemented rats developed a DU whereas 74% of rats fed standard Chow had DUs. Most rats had a single DU in the first part of the duodenum, occasionally a second ulcer was noted in the same area. Dietary supplementation with Vit. A had no effect on gastric acid production. In conclusion, our data show that Vit. A dietary supplementation is effective in preventing formation of DUs caused by cysteamine-HCl administration to rats. This effect does not appear to be due to reduction of gastric acid output.