The present study examines the involvement of acidosis in stress ulceration in rat stomachs. Cold restraint stress for 2 hr did not affect the blood lactate level; however, it produced respiratory acidosis, as reflected by the depressed respiratory rate which was associated with increased CO2 tension and a lowered blood pH. Severe hemorrhagic ulceration was found in the glandular mucosa. The effects of stress on blood pH and the stomach were reversed by IV infusion of NaHCO3. Infusion of HCl IV decreased the blood pH and HCO-3 level and produced gastric ulceration. It is concluded that respiratory acidosis could be involved in stress ulceration. The metabolic acidosis evoked by HCl also induced gastric damage, but the effect was much less.