AbstractOmega‐3 fatty acids, which are contained in fish oils and certain vegetable oils in contrast to corn oil or safflower oil rich in omega‐6 fatty acids (linoteic acid), have been reported to reduce the carcinogenesis in several organs. In this study, the modifying effect of menhaden fish oil was investigated on the occurrence of azoxymethane (AOM)‐induced glutathione S‐transferase placental form (GST‐P) positive hepatocellular foci, recognized preneoplastic lesions in the liver, in male F344 rats. Starting at five weeks of age, groups of animals were fed ad libitum a semipurified diet containing 5% corn oil (low fat). At seven weeks of age, all animals except the vehicle‐treated groups were injected subcutaneously with AOM (15 mglkg body wt, 1×lwk for 2 wks). Four days after the second injection, groups of animals were fed the diets containing 4% menhaden oil + 1% corn oil (low fish oil diet), 22.5% menhaden oil + 1% corn oil (high fish oil diet), and 5% corn oil. Thirty‐four weeks after AOM injections, all animals were necropsied. Livers were sectioned and performed immunohistochemical staining of GST‐P for quantitative analysis of enzyme altered foci of the liver. The results demonstrate that the density and the unit area of AOM‐induced enzyme altered foci in the liver were significantly lower in the high fish oil group (0.60±0.08/cm2, 3.0±0.4×10−4) than in the 5% corn oil group (2.71±0.33/cm2, 16.6±2.6×10−4) and the low fish oil group (1.66±0.33/cm2, 11.1±1.9×10−4). The denisty and the unit area of foci in the low fish oil group were lower than in the 5% com oil group, without statistical difference. The size of foci was also reduced in the high fish oil group, but the significant relationship could not be observed among the groups. These results indicate that fish oil rich in highly polyunsaturated omega‐3 fatty acids could modulate the occurrence of AOM‐induced GST‐P positive foci in rats.