This study was designed to investigate the role of lipid peroxidation in the pathogenesis of renal dysfunction in glutathione (GSH)-depleted rats. Renal function parameters and acid-base status were analyzed in diethylmaleate (DEM)-treated rats previously injected with vitamin E (Vit.E). Vit.E was effective in inhibiting the elevation in renal lipid peroxidation found in GSH-depleted rats. Vit.E also ameliorated the renal response to the metabolic acidosis without modification in lactate production induced by DEM administration. The increase in sodium and water urine excretion and the diminution of the urine to plasma osmolalities ratio were not reversed in these animals. These results lead us to conclude that lipid peroxidation is associated with distal acidification impairment observed with GSH-depletion, but it is not related to the sodium reabsorption alteration in the ascending loop of Henle.