Nitric oxide (NO) contributes to the extracellular potassium-ion concentration ([K⁺]_o)-induced hydroxyl radical (^•OH) generation. Cytotoxic free radicals such as peroxinitrite (ONOO⁻) and ^•OH may also be implicated in NO-mediated cell injury. NO is synthesized from L-arginine by NO synthase (NOS). NOS activation was induced by K⁺ depolarization. Oxidative modification of low-density lipoprotein (LDL) is thought to contribute to the production of oxygen derived-free radicals. However, LDL oxidation may be related to noradrenaline-induced ^•OH generation, but LDL oxidation may be unrelated to ^•OH generation via NOS activation. Abnormal levels of extracellular free dopamine (DA) and/or intraneuronal Ca²⁺ triggered by 1-methyl-4-phenylpyridinium ion (MPP⁺) may be detrimental to the functioning of dopaminergic nerve terminals in the striatum. Although [K⁺]_o-induced depolarization enhances the formation of ^•OH product due to MPP⁺, the ^•OH generation via NOS activation may be unrelated to the DA-induced ^•OH generation. Depolarization enhances the formation of ^•OH products via NOS activation.