NSAIDs are the most prescribed drugs for inflammation, and their use is associated with severe gastrointestinal toxicity. This work focuses on the interaction of NSAIDs with membranes, specifically, on their ability to affect the lipid dynamic properties, since this may explain the compromising effects on the integrity of gastric barrier. Studies covered the assessment of drug-membrane/water partition coefficient and location by derivative spectroscopy and fluorescence quenching techniques and effects on membrane biophysics by DSC. Results indicate that the NSAIDs studied have membrane destabilizing effects, which could be transposed to similar effects in the stomach's phospholipid layer justifying their toxicity. (C) 2009 Published by Elsevier B. V.