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The gastric toxicity of racemic-ketoprofen and its enantiomers (S(+)− and R(−)−ketoprofen), oxygen free radical generation and neutrophil infiltration in response to damage were evaluated in rats. Changes in prostaglandin synthesis, cyclooxygenase expression and glutathione metabolism were also studied. Studies were performed in Wistar rats. Drugs were given by oral administration: racemic-ketoprofen (100, 50 and 25 mg/kg body weight); S(+) and R(−)−ketoprofen (50, 25 and 12.5 mg/kg body weight). Determinations were made of gastric mucosal injury, lipid peroxidation, xanthine oxidase, myeloperoxidase and superoxide dismutase activities, glutathione levels, glutathione peroxidase and glutathione reductase activities, gastric prostaglandin synthesis (PGE2 levels) and COX-expression. Racemic-ketoprofen dose-dependently exhibited the highest toxicity. In contrast, S(+)−ketoprofen at half the dose of the racemic compound proved to be less ulcerogenic. R(−)−ketoprofen was also less ulcerogenic, but when administered as the racemate exacerbated gastric ulcération caused by S(+)−ketoprofen. Drug administration produced significant increases in lipid peroxidation levels and xanthine-oxidase and a decrease in Superoxide dismutase activity. Nevertheless the racemate induced the highest disturbances in oxidative metabolism. No changes in myeloperoxidase values and glutathione metabolism were found. Cyclooxygenase-1 immunoreactivity was observed and did not differ from that in control rats. Cyclooxygenase-2 could also be expressed after treatments. [ABSTRACT FROM AUTHOR]