Modulating effects of high fat fish oil (HFFO) and high fat corn oil (HFCO) diets on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) were studied in male F344 rats following 8 weeks of dietary treatment. The incidence of AOM-induced ACF was significantly lower in the proximal colon of rats fed the HFFO diets compared with rats fed the HFCO diets. No differential effects were found on enzyme activities that are involved in metabolic activation and detoxification of AOM. Activities of hepatic P450 IAI and P450 IIBI and hepatic and feacal levels of lipid peroxidation were increased by feeding the HFFO diet. Hepatic GST activity and plasma levels of PGE2 were significantly lower in rats fed the HFFO diets compared with those fed the HFCO diets. These observations demonstrate that HFFO diets with high levels of n-3 PUFAs are also protective against preneoplastic lesions in the early stages of chemically induced colon carcinogenesis. It seems unlikely from our results that the inhibitory effect of a HFFO diet can be attributed to an altered metabolic activation and detoxification of AOM. Other mechanisms such as oxidative stress or reduction of PGE2 levels may play an important role in the anticarcinogenic effects of n-3 PUFAs. © 2003 Elsevier Ltd. All rights reserved.