The effect of nimesulide on red blood cell (RBC) lysis photosensitized by tiaprofenic acid was investigated. The tiaprofenic acid-induced photohemolysis rate was enhanced by exposure to oxygen but lysis was also observed under anaerobic conditions. Photohemolysis was decreased by reduced glutathione (GSH) and reduced even more by butylated hydroxyanisole (BHA); sodium azide, superoxide dismutase and mannitol did not show a significant effect. Nimesulide did not cause any RBC lysis and inhibited this action of tiaprofenic acid by 20-30%, depending on the concentration of nimesulide and the intensity of ultraviolet A light. The protective effect of GSH, but not of BHA, was increased by nimesulide. Our findings suggest that free radicals are generated in this in vitro model of phototoxicity and are involved in the photoaggression to the red blood cell membrane, this effect being partially inhibited by nimesulide.