Salicylic acid (SA), a weak inhibitor of the prostaglandin endoperoxide synthetase or fatty acid cyclooxygenase enzyme, is known to prevent irreversible enzyme inhibition by acetylsalicylic acid (ASA). The interaction of arachidonic acid with ferrous sulfate was used as a model to study the reaction of the fatty acid with the postulated enzymic cationic binding site on Fe2+-heme. SA was as potent as ASA in inhibiting the cooxygenation of arachidonic acid and ferrous sulfate. The result suggests that SA could compete effectively for the enzyme cationic site with ASA. Thus SA may block ASA acetylation of the cyclooxygenase by preventing ASA from binding to this site.