NSAID intake is a frequent cause of development of gastroduodenal ulcers. The objective was to assess the effect on carbonic anhydrase (CA) of gastric antisecretory medication associated to Indomethacin. The study was conducted after dose-response relation in vitro-on CA I, II and IV and in vivo on 100 patients. The results shown the activator effect of Indomethacin, both in vitro and in vivo, on CA I, II and IV isoenzymes, which is correlated in vivo with gastric acid secretion increase. In the case of Omeprazole, inhibitory effect on the enzymatic activity of CA isozymes is more pronounced compared to the Ranitidine effect. The equimolecular association of NSAID with antisecretory medication reduces their inhibitory effect on isozymes I, II, IV of CA, which could explain gastric ulcerations occurrence after long treatment with NSAIDs, even if they are associated with antisecretory therapy