This work was carried out to estimate the preventive effect of vitamin E on oxy radical-enhanced lung tumorigenesis in ddY mice. We have reported that oxy radicals could be an important factor contributing to the promotive effect of glycerol on 4-nitroquinoline 1-oxide (4NQO)-induced lung tumorigenesis (1). The glycerol-promoted lung tumorigenesis of mice treated with 4NQO was reduced in mice feeding on excessive vitamin E in this study. The levels of nuclear thiobarbituric acid reactive substances (TBARS) and oxidative damage of DNA estimated as DNA single strand breaks (DNA-SSB) were significantly higher in the lungs of mice treated with 4NQO + glycerol than in those treated with 4NQO at 4 weeks after 4NQO administration, This increase was suppressed by the feeding of excessive vitamin E for 4 weeks after 4NQO injection. At 23 weeks after 4NQO injection, the feeding of excessive vitamin E for 4 and 23 weeks after 4NQO injection could cancel the promotive effect of glycerol on lung tumorigenesis. Additionally, the alpha-tocopherol level in serum was related with the degree of lung tumorigenesis at 23 weeks after 4NQO injection. These findings suggest that vitamin E can act as a useful agent to protect mice from oxy radical-promoted lung tumorigenesis.