The hydroxamic acid siderophore ferrioxam- Nitric oxide (NO), a short-lived potent vasodilator, was first described as the endothelium-derived relaxation factor (EDRF) (1-3). The formation of NO from the guanidino nitrogen group of L-arginine is catalyzed by a group of enzymes termed constitutive (cNOs) and inducible (iNOs) NO synthases (3,4). The inducible form is not present constitutively in mammalian cells but is induced by proinflammatory stimuli such as bacterial lipopolysaccharide (LPS), Corynebacterium parvum, and the cytokines tumor necrosis factor-a, interleukin-1, or interferon-y, individually or in combination (5). Excess production of NO is reported to be associated with the development of hypotension associated with endotoxemia and sepsis (6-8).Inhibition of iNOs is a potential therapeutic approach to the treatment of septic shock (6-9). However, mechanisms to protect against the deleterious effects of NO overproduction constitute an alternative approach. For instance, free hemoglobin can scavenge NO and inhibit its biological effects (10). In LPS-treated mice, formation of a paramagnetic mononitrosyl iron complex with diethyldithiocarbamate (NO Fe DETC) was detected and characterized by electron paramagnetic resonance (11). The NO formed in this animal model was trapped with endogenous Fe2+ complexed with a considerable amount (500 mg/kg) of DETC that was administered to the animals during the course of the experiment (11). Mortality was not addressed in this study. On the other hand, administration of vitamin B12A to mice prevented and reversed endotoxinmediated hypotension and decreased mortality, possibly through binding of the vitamin with excess NO (12). Inhibition of several actions of NO, including protection of rats against endotoxin, was demonstrated with the NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazolineoxyl-i-oxyl 3-oxide (13). We and others have characterized the in vivo models of induction of iNOs in mice and rats injected with C. parvum or C. parvum + LPS (14-18). We postulated that iron complexes could act as general NO scavengers and provide protection against septic shock. We screened a library of metal chelators and chelates and found that [Fe(III)