Nitric oxide (^•NO) is a physiological, free radical messenger found within the central nervous system (CNS) and other tissues. Its ability to activate guanylate cyclase, and hence to increase cyclic GMP levels suggests that ^•NO may be involved in a large number of intracellular processes. Regardless of the role of cyclic GMP as a mediator of the effects of ^•NO, this species is directly involved in the regulation of important cellular functions. Reversible inhibition of mitochondrial respiration caused by ^•NO by competing with O₂ for cytochrome c oxidase might contribute to balancing cellular energy status. Under certain conditions, however, brain ^•NO synthesis might be exacerbated, the compound thus becoming a potent neurotoxic agent. In this sense, the reaction of ^•NO with superoxide anion (O₂^•¯) produces an unstables species, peroxynitrite anion (ONOO¯), which appears to be directly responsible for the specific and irreversible impairment of the mitochondrial respiratory chain, leading to cellular energy deficiency. The possible mechanisms explaining the pathophysiological roles of ^•NO in the energy metabolism of CNS cells are discussed.