The effect of zinc sulphate on stomach ulceration produced by ethanol and indomethacin was examined in rats. Oral or intraperitoneal pretreatment with zinc sulphate (20 mg/kg, expressed as zinc ion) strongly prevented ethanol-, but not indomethacin-induced gastric glandular ulceration. Indomethacin given beforehand did not influence the protective action of zinc sulphate against ethanol-evoked lesions. Ethanol decreased histamine levels, whereas indomethacin reduced the prostaglandin E2 (PGE2) content in the gastric glandular mucosa. The alcohol also elevated the histamine content in gastric secretion. Zinc sulphate reversed the ethanol-induced changes in histamine levels in both mucosa and secretion, but did not modify PGE2 reduction by indomethacin. Zinc sulphate also antagonised protein leakage from the stomach following ethanol administration. It is concluded that gastric ulceration by the currently employed doses of ethanol and indomethacin is caused by different mechanisms. Zinc sulphate prevents histamine-mediated lesions produced by the alcohol, but not ulceration due to PGE2 depletion by indomethacin.