Nitric oxide originating from the microvascular endothelium and other tissue sources appears to play an important physiological role in the regulation of mitochondrial respiration in vivo. Physiological processes and pathophysiological conditions that influence the production and action of nitric oxide are likely to alter the control of tissue respiration by nitric oxide. Oxidant stress associated with the production of peroxynitrite from nitric oxide, under conditions such as hypoxia-reoxygenation, convert the reversible inhibition of respiration by nitric oxide into an irreversible process, which is potentially an important contributor to the expression of alterations in physiological function and tissue injury.