Oxidized ATP (oATP) is a Schiff-base-forming reagent that has been used for some years as an antagonist at the P2X7 receptor (P2X7R). Preincubation of mononuclear phagocytes with this inhibitor leads to attenuation of several proinflammatory responses triggered by extracellular ATP as well as a few non-nucleotide agonists. Novel data show that oATP reduces NFkappaB activation and IL-8 release in cells lacking P2X7R, thus suggesting that some anti-inflammatory effects of oATP may not be due to blockade of the P2X7R. This effect of oATP resembles the action of other natural or synthetic Schiff-base-forming reagents with immunomodulatory activity.