Ethanol withdrawal is a serious clinical problem owing in part to over stimulation of ionotropic glutamate receptors in the brain and is linked to elevated oxidative damage. In this study, we tested the hypothesis that lipid peroxidation is elevated in the brain tissue of rats fed an ethanol-containing diet for 6 weeks followed by 24h of withdrawal. We measured F(2)-isoprostanes (IsoPs), as products of arachidonic acid (20:4, n-6) oxidation and F(4)-neuroprostanes (NeuroPs), as products of docosahexaenoic acid (22:6, n-3; DHA) oxidation. Levels of NeuroPs were significantly elevated in the cerebral cortex (97%) and brainstem (68%) of animals undergoing ethanol withdraw versus control. In contrast, elevations in IsoP content (39%) occurred only in the cerebellum of animals in withdrawal versus control animals. These data demonstrate that DHA, versus arachidonic acid, is particularly vulnerable to oxidative damage in ethanol withdrawal.