The effect of (n-3) fatty acid supplementation on cytokine production and lymphocyte proliferation was investigated in young (23-33 y) and older (51-68 y) women. Subjects supplemented their diets with 2.4 g of (n-3) fatty acid/d for 3 mo. Blood was collected before and after 1, 2 and 3 mo of supplementation. The (n-3) fatty acid supplementation reduced total interleukin (IL)-1 beta synthesis by 48% in young women but by 90% in older women; tumor necrosis factor was reduced by 58% in young and 70% in older women. Interleukin-6 was reduced in young women by 30% but by 60% in older women. Older women produced less IL-2 and had lower mitogenic responses to phytohemagglutinin (PHA) than young women prior to (n-3) fatty acid supplementation. The (n-3) fatty acid supplementation reduced IL-2 production in both groups; however, this reduction was significant only in older women. The PHA-stimulated mitogenic response was significantly reduced by (n-3) fatty acid in older women (36%). Thus, long-term (n-3) fatty acid supplementation reduced cytokine production in young women and cytokineproduction and T cell mitogenesis in older women. The reduction was more dramatic in older women than in young women. Although (n-3) fatty acid-induced reduction in cytokine production may have beneficial anti-inflammatory effects, its suppression of IL-2 production and lymphocyte proliferation in older women may not be desirable.