CONGENERS of nitrogen monoxide (NO) are neuroprotective and neurodestructive^{1– 7.} To address this apparent paradox, we considered the effects on neurons of compounds characterized by alternative redox states of NO: nitric oxide (NO^.) and nitrosonium ion (NO⁺)⁸. Nitric oxide, generated from NO^. donors or synthesized endogenously after NMDA (N-methyl-D-aspartate) receptor activation, can lead to neurotoxicity^3,4. Here, we report that NO^.-mediated neurotoxicity is engendered, at least in part, by reaction with superoxide anion (O^.-₂), apparently leading to formation of peroxynitrite (ONOO−), and not by NO^. alone. In contrast, the neuroprotective effects of NO result from downregulation of NMDA-receptor activity by reaction with thiol group(s) of the receptor's redox modulatory site¹. This reaction is not mediated by NO^. itself, but occurs under conditions supporting S-nitrosylation of NMDA receptor thiol (reaction or transfer of NO⁺). Moreover, the redox versatility of NO allows for its interconversion from neuroprotective to neurotoxic species by a change in the ambient redox milieu. The details of this complex redox chemistry of NO may provide a mechanism for harnessing neuroprotective effects and avoiding neurotoxicity in the central nervous system.