Nitric oxide is a simple free radical with pivotal roles in cell regulation and function (1). The interaction between nitric oxide and the superoxide radical results in the formation of peroxynitrite1 (2), particularly during episodes of excessive production of nitric oxide and/or superoxide. The formation of peroxynitrite, as originally proposed by Beckman et al.(3), has been linked to pathology. Research efforts directed to understand the mechanism of reaction of peroxynitrite were initially focused primarily on the reactions of peroxynitrite with substrates with zero order kinetics (eg, dimethyl sulfoxide and deoxyribose), with substrates with relatively small second-order rate constants (eg, methionine and ascorbate), and even a few more reactive substrates, such as thiols (3-6). Although these experiments afforded important mechanistic information, the reactions of peroxynitrite with these substrates cannot compete with the reaction of peroxynitrite with CO2 under physiological conditions. The fast reaction between peroxynitrite and bicarbonate buffers was first reported by Keith and Powell (7) but the implications of this observation were