Chronic ethanol feeding promotes oxidative stress in rat peripheral nerve. Malondialdehyde, a lipid peroxidation product, content increases in sciatic nerves of rats fed an ethanol-containing diet, when compared with pair-fed animals. Moreover, glutathione content and glutathione peroxidase activity in this same tissue decrease in ethanol-fed vs. pair-fed rats. S-Adenosyl-L-methionine and N-acetyl-L-cysteine, both with possible therapeutic action on alcoholism, were tested in this animal model. Only N-acetyl-L-cysteine was able to normalize malondialdehyde content and to restore glutathione content and glutathione peroxidase activity, to values not significantly different from those of sciatic nerves from pair-fed animals. The reasons for the different effect of both substances tested is also discussed.