In vitro activity: 4-Aminosalicylate reacts promptly with DPPH, suggesting a potent radical scavenger activity. 4-Aminosalicylate exhibits peroxyl radical scavenging activity generated by the water-soluble 2,2'-azobis-(2-amidinopropane hydrochloride) azoinitiator of peroxyl radicals, as evidenced by the inhibition of cis-parinaric acid fluorescence decay or oxygen consumption. 4-Aminosalicylate rapidly scavenges peroxyl radicals in the aqueous phase, producing a concentration-dependent inhibition period similar to Trolox or cysteine, suggesting an antioxidant activity of chain-breaking type. [14C]4-Aminosalicylate transforms to a number of metabolites, among which we have characterized salicylate and gentisate, in activated mononuclear cells and activated granulocytes. 4-Aminosalicylate (0.65 mM) diminishes the lethal effect on cultured Chinese hamster ovary cells of adding either superoxide radical or hydrogen peroxide. Aminosalicylate (25 mM) stimulates phospholipase D in a time- and concentration-dependent manner via a pathway involving inositol 1,4,5-trisphosphate generation, calcium fluxes, and Gi/Go in cultured mouse peritoneal macrophages. 4-aminosalicylate (20 mM) increases the levels of inositol 1,4,5-trisphosphate by 260% after treatment of macrophages. 4-aminosalicylate (5 mM) potentiates the activation of PLD by protein kinase C in cultured mouse peritoneal macrophages.