Nitric oxide is a double-edged sword. Produced by mammalian cells at an appropriate magnitude and tempo, it serves as a key signaling molecule in physiological processes as diverse as host-defense, neuronal communication, and vascular regulation (for reviews, see 131, 132, 172). On the other hand, excessive and unregulated NO synthesis has been implicated as causal or contributing to pathophysiological conditions induding many lethal and de bilitating diseases of humans: vascular shock, stroke, diabetes, neurodegenera tion, arthritis, and chronic inflammation. Contrary to conventional biosignaling molecules that act by binding to specific receptor molecules, NO manifests its biological actions via a wide range of chemical reactions. NO is a small, relatively stable, free-radical gas that readily diffuses into cells and cell mem branes where it reacts with molecular targets. The precise reactions, which are realized in any biological setting, depend on the concentration of NO achieved and often on subtle variations in the composition of the intra-and extracellular milieu. This review summarizes the present knowledge of cellular events that lead to NO overproduction in mammalian systems and discusses reactions of NO that may contribute to cell damage or death. Our primary aim is to interpret rather than exhaustively summarize the large body of accumulated NO litera-