Dietary fat has been shown to exert a wide variety of actions that result in enhanced mammary and colon tumorigenesis. Such a range of mechanisms suggests the involvement of intermediary or secondary messenger molecules. Eicosanoids, produced from arachidonic acid (C20:4, n-6), are known to have various effects on physiological and biochemical events. The production of these dienoic eicosanoids is controlled during normal physiological events, but excessive quantities of some products are produced in some pathological conditions such as cancer. Often dienoic eicosanoids affect some of the same processes that are influenced by dietary fat, such as linoleic acid (C18:2, n-6). Therefore, eicosanoids may represent a potential system for mediating or modulating the effect of a linoleate-rich diet. The feeding of fish oil has resulted in decreased concentrations of linoleic and arachidonic acids and increased concentrations of eicosapentaenoic acid (C20:5, n-3) and docosahexaenoic acid (C22:6, n-3). Both eicosapentaenoic and docosahexaenoic acids antagonize the production of eicosanoids from arachidonic acid. We have examined the effects of fish oil on the growth of the R3230AC mammary adenocarcinoma, the 7,12-dimethylbenz[a]-anthracene-induced mammary tumors, and the DU-145 human prostatic tumor. Although the precise mechanisms of action are unclear, currently available data suggest that eicosapentaenoic acid + docosahexaenoic acid, at an optimal ratio of n-3/n-6 fatty acids, may have protective effects against development and/or progression of the tumor models studied.