Ochratoxin A (OTA), is a nephrotoxic mycotoxin present in wine, which is nephrotoxic in humans. Our working hypothesis is that natural substances in wine may counteract OTA toxicity. Thirty-six rats were randomized to OTA dissolved in saline, red wine, or 13.5% ethanol or to OTA-free wine, ethanol, or saline. OTA (289 microg/kg of body weight/48 h) was administered by gastric gavage for 2 weeks. Serum creatinine, tubular enzymuria, renal lipohydroperoxides (LOOH), reduced (GSH) and oxidized (GSSG) glutathione, and renal superoxide dismutase activity (SOD) were determined in renal tissue. OTA alone produced significant increases in renal lipoperoxides and significant decreases in SOD and GSH/GSSG ratio. In red wine or ethanol, OTA was less nephrotoxic, reducing oxidative damage as revealed by LOOH. In OTA-wine and OTA-ethanol groups, SOD activity was higher than in the OTA-treated one, suggesting that both ethanol and nonalcoholic fractions may preserve antioxidant reserve. GSH/GSSG ratio was significantly preserved only in the OTA-wine group and not in OTA-ethanol. Red wine may exert a protective effect against OTA nephrotoxicity by limiting oxidative damage. The ostensible protection afforded by ethanol deserves further investigation.