1. The in vivo effects of the non-steroid anti-inflammatory drug (NSAID) amtolmetin guacyl (AMG) on lipid peroxidation (LP) and on antioxidant enzyme and non-enzyme defence systems were investigated in models of stomach and colon damages, induced by other NSAIDs, by ethanol or by 2,4,6-trinitrobenzenesulfonic acid (TNBS). 2. Indomethacin increased LP, glutathione peroxidase (GSH-PX) and glucose-6-phosphate dehydrogenase (Glu-6-P-DH) activities and decreased glutathione levels in gastric mucosa. Pretreatment with AMG normalized some of the parameters affected by indomethacin. 3. Treatment of rats with ethanol for 0.5 h led to a decrease in glutathione levels as well as activities of glutathione reductase and Glu-6-P-DH in gastric mucosa. AMG, administered 0.5 h before ethanol, limited the adverse actions of ethanol. 4. Amtolmetin guacyl failed to abolish the TNBS-induced changes in the followed-up parameters in colon mucosa and liver, but additional alterations (as with tolmetin) were not observed. 5. The beneficial profile of AMG in the various experimental models of free radical-induced damage investigated in this study suggests the possibility that this drug might possess antioxidant activity.