Abstract In this study, we investigated the effect of vitamin E on the activation of the K- ras oncogene with a 61st codon A→T mutation at an early stage of urethane-induced lung carcinogenesis in mice. Thirty days after urethane injection, the K- ras mutation was detected in 64% of lung samples tested by mutant-allele-specific amplification. The consumption of a supplemented diet with about 20-times more vitamin E than the control diet, only during the promotion phase or during both the initiation and promotion phases of lung carcinogenesis, reduced the frequency of the mutation to 36 and 18%, respectively. Also, vitamin E suppressed the level of proliferating cell nuclear antigen as a marker of cell proliferation in the lungs of mice treated with urethane. These results support the notion that vitamin E is a useful chemopreventive agent against lung cancer. © 1997 Elsevier Science B.V.