['Endogenous and exogenous prostaglandins (PGs) have been shown to contribute to reducing the gastric injury caused by irritants given subsequently. The aim of this study was to clarify whether cyclooxygenase-2 (COX-2) protein induced by pretreatment was involved in the prevention of subsequent ethanol-caused gastric injury in mice.', 'Mice were pretreated with acidified ethanol or saline and then COX-2 protein expression in the stomach was immunohistochemically determined every 8h. Mice were administered 95% ethanol 24h after the acidified ethanol pretreatment, and gastric mucosal damage was evaluated macroscopically and histologically. The effects of NS-398 or indomethacin on the 95% ethanol-caused damage were also examined.', 'Acidified ethanol pretreatment induced COX-2 protein expression in lamina propria macrophages of the gastric mucosa, with a peak level 24h after the pretreatment. The 95% ethanol treatment caused gastric mucosal damage. The degree of the damage was not different between mice pretreated with acidified ethanol and those pretreated with saline. However, NS-398 aggravated the ethanol-caused damage only in mice pretreated with acidified ethanol, while indomethacin aggravated the damage, evaluated histologically, irrespective of the pretreatment.'] Is irritant-induced cyclooxygenase-2 involved in the defense mechanism of the gastric mucosa in mice?