Nonsteroidal anti-inflammatory drugs (NSAIDs) represent non-specific inhibitors of the cycloxygenase pathway of inflammation, and therefore an understanding of the interaction process of these type of drugs with membrane phospholipids is of high importance. There are still many unresolved points about the exact molecular mechanismbehind the action of NSAIDs. The present study was designed to investigate the effects of two NSAIDs, namely sulindac and naproxen, on phospholipid membranes. The effects of sulindac and naproxen at various concentrations (1, 6, 9, 12, and 18 mol%) on phospholipid model membranes prepared from dipalmitoylphoshatidylcholine (DPPC)-Cholesterol has been studied by turbidity technique as a function of temperature (25 ºC Â 65 ºC; with 2 ºC intervals). Sulindac decreases the fluidity of the DPPC-cholesterol model membrane system at all temperatures studied, while naproxen increases the fluidity of the samemodelmembrane systemat lowtemperatures (below 40 ºC). Sulindac and naproxen alter the physicochemical properties of phospholipid membranes by changing the dynamics of the model membranes.