Copper-zinc superoxide dismutase (Cu,ZnSOD) is the antioxidant enzyme that catalyzes the dismutation of superoxide (O 2 •− ) to O 2 and H 2 O 2 . In addition, Cu,ZnSOD also exhibits peroxidase activity in the presence of H 2 O 2 , leading to self-inactivation and formation of a potent enzyme-bound oxidant. We report in this study that lipid peroxidation of l -α-lecithin liposomes was enhanced greatly during the SOD/H 2 O 2 reaction in the presence of nitrite anion (NO 2 − ) with or without the metal ion chelator, diethylenetriaminepentacetic acid. The presence of NO 2 − also greatly enhanced α-tocopherol (α-TH) oxidation by SOD/H 2 O 2 in saturated 1,2-dilauroyl-sn-glycero-3-phosphatidylcholine liposomes. The major product identified by HPLC and UV-studies was α-tocopheryl quinone. When 1,2-diauroyl-sn-glycero-3-phosphatidylcholine liposomes containing γ-tocopherol (γ-TH) were incubated with SOD/H 2 O 2 /NO 2 − , the major product identified was 5-NO 2 -γ-TH. Nitrone spin traps significantly inhibited the formation of α-tocopheryl quinone and 5-NO 2 -γ-TH. NO 2 − inhibited H 2 O 2 -dependent inactivation of SOD. A proposed mechanism of this protection involves the oxidation of NO 2 − by an SOD-bound oxidant to the nitrogen dioxide radical ( • NO 2 ). In this study, we have shown a new mechanism of nitration catalyzed by the peroxidase activity of SOD. We conclude that NO 2 − is a suitable probe for investigating the peroxidase activity of familial Amyotrophic Lateral Sclerosis-linked SOD mutants.