The effect of acute ethanol consumption on plasma glutathione (GSH) and malondialdehyde (MDA) concentrations was studied in two groups of healthy male subjects. The first group (n = 15) received an acute dose of ethanol (1.5 g/kg p.o. over a period of 3 h); in the control group (n = 15), ethanol was replaced isocalorically with carbohydrates. Blood samples were taken at 0 time (ethanol/carbohydrates ingestion) and every 60 min for 6 h. A significant increase in plasma MDA concentration as well as in plasma GSH values were observed in subjects receiving ethanol compared to controls. The enhancement of plasma GSH was accompanied by a concomitant increase of oxidized glutathione (GSSG). These data support the hypothesis of an increase of lipid peroxidation as a possible mechanism of acute ethanol toxicity. The enhancement of plasma GSH and GSSG may reflect an increased utilization and loss of the tripeptide from the liver induced by ethanol.