Our study was undertaken to assay gentisate, an oxidation metabolite of salicylate, in plasma and synovial fluid (SF) samples from patients taking antiinflammatory doses of aspirin. A close correlation between plasma and SF concentrations was found for (1) salicylate, (2) salicylurate, and (3) gentisate, in 20 patients studied. Our data suggest ready equilibration of these compounds between the plasma and synovial spaces. In vitro experiments confirmed that in the presence of an oxy radical flux, salicylate is oxidized to gentisate. However, no evidence was obtained to implicate peripheral conversion of salicylate to gentisate in inflamed joints where oxy radicals may be produced.