The inhibitory effect of dietary perilla oil rich in the n-3 polyunsaturated fatty acid alpha-linolenic acid against colon carcinogenesis was investigated in rats. Four groups of 26 F344 rats each received an intrarectal dose of 2 mg of N-methyl-N-nitrosourea 3 times a week for 2 weeks, and received a diet containing 12% perilla oil, 6% or 12% safflower oil (rich in the n-6 polyunsaturated fatty acid linoleic acid), or 12% palm oil (rich in saturated and monounsaturated fatty acids). At week 35, the incidence of colon cancer was significantly lower in perilla oil-fed rats than in other dietary groups; 19% vs. 46%, 56% and 58%. When examined at week 10, the concentration of fecal bile acids, known to be tumor promoters, was not significantly different among the dietary groups, and the intrarectal deoxycholic acid-induced colonic mucosal ornithine decarboxylase activity, a marker of tumor promotion, was significantly lower in perilla oil-fed group than in other groups. The serum and colonic mucosal fatty acid compositions and the blood plasma prostaglandin E2 level directly reflected the fatty acid composition of each dietary fat. The results suggest that the anti-tumor-promoting effect of dietary perilla oil was a result of a decreased sensitivity of colonic mucosa to tumor promoters arising from the altered fatty acid composition in membrane phospholipid of colonic epithelial cells, and was not a consequence of a decrease of promoters such as bile acids.