Using a novel spectrophotometric assay to detect free radical scavengers, the effects of sulfasalazine, a compound frequently administered in the treatment of chronic inflammatory bowel disease, and its main metabolites, 5-aminosalicylic acid (5-ASA), sulfapyridine, and N-acetyl-5-ASA, were compared with biological antioxidants (nordihydroguaiaretic acid (NDGA), alpha-tocopherol, and ascorbic acid) and antiinflammatory salicylates (acetylsalicylic acid and sodium salicylate). The results show that 5-ASA, but neither sulfasalazine and its other metabolites, nor the salicylates, shares with the biological antioxidants the property of being a potent scavenger of free radicals. Since 5-ASA is formed in millimolar concentrations in the colon of sulfasalazine-treated patients this mode of action may explain the beneficial effect of sulfasalazine in inflammatory bowel disease. Locally formed 5-ASA may break the free radical chain reaction initiated and maintained by activated phagocytes, thus arresting the perpetuating tissue destruction. This mechanism may indicate a general potential for radical scavengers in chronic inflammation.