Eleven patients with rheumatoid arthritis (RA) were treated with intraarticular deferoxamine or placebo to test the hypothesis that iron chelation decreased hydroxyl radical mediated lipid peroxidation in RA. Intraarticular administration of deferoxamine 100 mg resulted in predominantly systemic effects with decreased serum ferritin and decreased serum levels of lipid peroxidation products. Similar changes were not detected in synovial fluid at this dose. Iron chelation with deferoxamine may provide a novel approach to preventing tissue injury in RA by inhibiting hydroxyl radical production and lipid peroxidation.