Local intra-arterial infusion of high doses of nitric oxide (NO) donors, such as S-nitroso-N-acetyl-penicillamine or nitroprusside cause extensive gastric mucosal damage. The involvement of lipid peroxidation of mucosal tissue in the mechanism of such gastric damage has been investigated in the pentobarbitone-anaesthetised rat. Local intra-arterial infusion of nitroprusside (40 micrograms.kg-1.min-1) or S-nitroso-N-acetyl-penicillamine (40 micrograms.kg-1.min-1) induced macroscopically apparent injury and provoked a dose-dependent peroxidation of lipid in gastric tissue. By contrast, endothelin-1 infusion provoked mucosal injury of the mucosa, yet did not produce lipid peroxidation. Local co-infusion of superoxide dismutase (2000-4000 IU.kg-1) reduced both the lipid peroxidation and the mucosal damage provoked by S-nitroso-N-acetyl-penicillamine and nitroprusside. These findings indicate that lipid peroxidation accompanies the mucosal tissue damage induced by NO donors, while the action of superoxide dismutase implicates the involvement of peroxynitrite, formed from superoxide and NO, in this process.