1. There is good evidence that acid is a prerequisite for aspirin induced gastric mucosal damage; however, there is inconsistent information available for non-salicylate NSAID. The present study examines the effect of gastric luminal pH on indomethacin-induced gastric mucosal damage. 2. Macroscopic gastric mucosal damage induced by indomethacin (40 mg/kg) or vehicle, administered intraduodenally to male pylorus-ligated rats (n = 5-10/group), was assessed at four different levels of luminal pH (2,4,5.5 and 7) by means of digital planimetry. 3. There was a marked difference in the extent of damage induced by indomethacin at the different luminal pH levels (P = 0.001). There was no difference between the percentage of haemorrhagic lesions at pH 2 and 4 (P > 0.05), nor between pH 5.5 and 7 (P > 0.05). However, the damage at the high levels of luminal acidity (pH 2 and 4) was strikingly different from that at pH 5.5 and 7 (P < 0.05). 4. Gastric mucosal damage induced by indomethacin, a non-salicylate NSAID, is augmented by the presence of high concentration of acid in the gastric lumen. The main finding, that indomethacin injury is markedly less above pH 4, may have clinical implications in the prevention of NSAID-induced mucosal injury.