Cytokines are important biologic mediators with tightly regulated production. Overproduction contributes to pathogenesis of acute and chronic inflammatory, autoimmune, atherosclerotic, and neoplastic diseases. Animal and human studies have shown that production of cytokines can be reduced by long-chain (n-3) polyunsaturated fatty acids (PUFA). This, in turn, results in reduction of the severity of certain autoimmune, inflammatory, and atherosclerotic diseases and reduces cytokine-induced anorexia. Because these cytokines are also involved in control of the host defense, substantial reduction in their production could impair normal immune response. In addition, increased intake of (n-3) PUFAs without adequate antioxidant protection could result in increased free radical formation and lipid peroxidation, leading to a reduction in T cell-mediated function, natural killer cell activity, and macrophage cytotoxicity. These risks associated with the intake of (n-3) PUFAs may be minimized without compromising its beneficial effects by the intake of appropriate levels of antioxidants such as vitamin E.