The potential role of iron in cerebral vasospasm was examined in the rat femoral artery model by the perivascular application of deferoxamine, a ferric ion chelator and antioxidant. In 25 rats, platelet-rich plasma or fresh autologous whole blood containing deferoxamine at concentrations of 1, 5, 10, or 15 mg/ml was applied to the adventitial surface of the femoral artery in a Silastic cuff to insure chronic exposure to the vessel wall. At 7 days, contralateral femoral arteries exposed to whole blood showed a 70% reduction in luminal cross-sectional area and morphological changes associated with vasospasm. Application of platelet-rich plasma or whole blood containing deferoxamine at 25 mg/ml produced no significant arterial narrowing or structural changes; significant intermediate reductions in arterial narrowing were observed at deferoxamine concentrations of 5 and 10 mg/ml. Presaturation deferoxamine (10 mg/ml) with excess ferric ion prior to application eliminated the protective effect. In addition, deferoxamine chelated the ferric ion released from incubated whole blood in vitro over 7 days in a dose-dependent manner consistent with its protective effect in vivo. Ferric ion may influence the development of chronic arterial narrowing after subarachnoid hemorrhage by a variety of mechanisms.