The study was aimed at investigating vitamin E and vitamin C concentrations in a liver and kidney as well as their involvement in the mechanism of peroxidative action of lead (Pb) and ethanol (EtOH) in these organs in rats receiving 500 mg Pb/l (in drinking water) or/and 5 g EtOH/kg body wt./24h (p.o.) for 12 weeks. The exposure to Pb and EtOH alone and in combination led to a decrease in vitamin E concentration in the liver compared to the control group (by 30%, 26% and 50%, respectively). The decrease in the liver vitamin E concentration in the rats co-exposed to Pb and EtOH was more marked than in those separately treated with these xenobiotics. The treatment with Pb alone and in combination with EtOH led to a decrease in vitamin E concentration in the kidney (by 13% and 21%, respectively). The liver vitamin C concentration decreased as a result of exposure to EtOH, both separately (by 17%) and in combination with Pb (by 11%). The kidney vitamin C concentration increased in the rats exposed to EtOH alone (by 10%), whereas in those treated with Pb, both separately and in combination with EtOH it decreased (by 26% and 6%, respectively). ANOVA/MANOVA analysis revealed that the changes in vitamin E concentration in the liver and kidney at co-exposure to Pb and EtOH resulted from their independent action, whereas those in vitamin C were due to an independent action of these xenobiotics (EtOH in the liver, Pb and EtOH in the kidney) and an interaction between them. There was no correlation between vitamins E and C concentrations in the liver and kidney. The liver concentration of vitamin E and the liver and kidney concentration of vitamin C negatively correlated with malondialdehyde concentration (MDA, lipid peroxidation index) in these organs. Based on the results of the present study and our previous findings in this experimental rat model it can be hypothesized that vitamins E and C are involved in the mechanism of peroxidative action of Pb and EtOH in the liver and kidney, both at separate and combined exposure. The probable protective involvement of vitamins E and C in the damaging action of EtOH and Pb may be related to scavenging of free radicals directly and indirectly generated by these xenobiotics.