The modulating effect of dietary polyunsaturated fatty acids (PUFAs) on benzo(a)pyrene-induced forestomach tumorigenesis was assayed in mice fed with corn oil (CO), olein (O), Zizyphus mistol seed oil (MO), cod liver oil (CLO), and mixed fat (Stock diet). The fatty acid composition of liver lipids correlated well with the fatty acid composition of each diet. Only mice fed the O diet showed biochemical and clinical evidences of essential fatty acid deficiency (EFAD). Only 3 animals developed well-differentiated invading squamous cell carcinomas in the O group. The papilloma incidence was reduced in MO and CLO with respect to the O group. Forestomach papillomatosis was increased in mice fed an n-9 enriched diet in comparison to stock and CO groups. In comparison with stock mice, the frequency of multiple epidermoidal hyperplasia (MEH) was significantly decreased in the CLO group. Animals fed n-3 enriched diets (MO and CLO) showed significant antipromoting effect. These findings indicate that dietary fat can modulate tumorigenesis initiated in mouse forestomach by benzo(a)pyrene. In addition, the lack of action of an n-6 fatty acid-enriched diet in our experimental model suggests that the effect of PUFAs on tumorigenesis has target-tissue specificity. Mistol seed oil might be of potential value as a natural vegetable antipromoter nutrient.