Earlier studies have implicated reactive oxygen species and transitional metals in the pathogenesis of gastric lesions. In this study, we have evaluated the effect of 2,3-dimercaptopropanol (DMP), a thiol compound and metal chelator, on chemically induced gastroduodenal ulcers in rats. Acid secretion studies were undertaken using pylorus-ligated rats pretreated with DMP (3-100 mg/kg, i.p.). The effect of orally administered DMP on cysteamine-induced duodenal ulcers and ethanol-induced gastric ulcers was also tested. The level of nonprotein sulfhydryls (NP-SH) and gastric wall mucus was measured in the glandular stomach of rats treated with ethanol. None of the dose of DMP affected the volume or acidity of gastric secretion. Low doses of DMP (3 and 10 mg/kg) significantly reduced cysteamine-induced duodenal ulcers, whereas the high doses (30 and 100 mg/kg) were ineffective in this model. All the doses of DMP significantly and dose dependently attenuated ethanol-induced gastric lesions. The adverse effects of ethanol on gastric wall mucus and NP-SH were significantly and dose dependently reversed by DMP. In conclusion, the protective effects of DMP appear to be independent of gastric acid secretion and may be associated with counteracting the oxidative stress by replenishing glutathione and reducing the pool of transition metals.