Reactive oxygen species and reactive nitrogen species are mediators of lung tissue damage. To minimize the effect of oxidative stress, the lung is well equipped with an integrated antioxidant system. In some circumstances, antioxidants increase in response to oxidants and reduce tissue injury. The lung is somewhat unique in that it has an extracellular surface, which is often directly exposed to oxidative stresses. In this context, the extracellular antioxidant system, comprised primarily of glutathione and glutathione peroxidase, is especially important in protecting against oxidant injury. Induction of extracellular glutathione peroxidase occurs in airway inflammation and undoubtedly plays an important defense against oxidative injury to the airway surface.