This study was undertaken to estimate the effect of high-oleic peanut oil (HO) on the promotion stage of lung tumorigenesis in mice. On day 30 after methyl nitrosourea administration, dietary HO inhibited ornithine decarboxylase activity, induced the inactivation of Mek, and reduced the level of proliferating cell nuclear antigen in lungs of mice more than did high-linoleic safflower oil. A parallel effect was observed in the level of prostaglandin E2 in the lungs. These results suggest that HO suppresses the promotion stage of lung tumorigenesis in mice and that the suppression correlates to the level of PGE2.