It has been suggested that endogenous nitric oxide may act as a protective factor for gastric mucosa since nitric oxide increases blood flow and may scavenge certain oxyradicals. We tested the hypothesis that nitric oxide protects rat gastric mucosa against ischaemia-reperfusion stress. Gastric ischaemia was induced by clamping the left gastric artery for 20 min. Rats were treated with two kinds of specific inhibitors of nitric oxide production, NG-nitro-L-arginine or NG-monomethyl-L-arginine. Gastric mucosal integrity was continuously monitored by measuring the blood-to-lumen clearance of [51chromium]-labelled ethylenediaminetetraacetic acid (EDTA) under control conditions, during ischaemia and after reperfusion. Oxidative stress in gastric mucosa was assessed by measuring dichlorofluorescein (DCF) fluorescence intensity before ischaemia and after reperfusion. Blockade of nitric oxide resulted in a significant increase in [51Cr]-EDTA clearance and DCF fluorescence intensity after reperfusion. These effects of nitric oxide inhibitors were attenuated by pretreatment with L-arginine. In conclusion, these findings support the hypothesis that endogenous nitric oxide acts as an important protective factor against ischaemia-reperfusion stress in rat gastric mucosa.