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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 …