Many studies have shown that addition of fish oil (FO) to the diet reduces tumor growth but the mechanism(s) of action involved is (are) still unknown. In this study, we examine some possible mechanisms in tumor-bearing rats chronically supplemented with FO. Male Wistar rats (21 days old) were fed with regular chow and supplemented with coconut or FO (1g/kg body weight) until they reached 70 days of age. Then, they were inoculated with a suspension of Walker 256 ascitic tumor cells (2 x 10(7)ml) and after 14 days they were killed. Supplementation with FO resulted in significantly lower tumor weight, greater tumor cell apoptosis, lower ex vivo tumor cell proliferation, a higher tumor content of lipid peroxides, lower expression of cyclooxygenase-2 (COX-2) in tumor tissue and a lower plasma concentration of prostaglandin E2 than observed in rats fed regular chow or supplemented with coconut oil. These results suggest that reduction of tumor growth by FO involves an increase in apoptosis and of lipid peroxidation in tumor tissue, with a reduction in tumor cell proliferation ex vivo, COX-2 expression and PGE2 production. Thus, FO may act simultaneously through multiple effects to reduce tumor growth. Whether these effects are connected through a single underlying mechanism remains to be seen.