Calorie restriction or fish oil extends life span. To investigate the potential mechanism(s) involved, young (4-month) and old (9-month) NZB x NZW(F1) mice were fed 5% (w/w) corn oil (CA) or fish oil (FA) ad libitum or 40% restricted (CR and FR, respectively). Peripheral blood T-lymphocytes were analyzed for Th-1 (IL-2, IFN-gamma) and Th-2 (IL-5, IL-10) production. CR and FA partially blunted while FR completely abolished the decline in aged CD4+ T lymphocytes. In contrast, both CR and FR abolished the decline in CD8+ T lymphocytes with age, while FA had no effect. In aged mice, both CR and FR blunted the increase in Th-1 (IL-2, IFN-gamma) cytokine production, while FA was only partially effective. Only FR completely blunted the age-related increase in Th-2 (IL-5, IL-10) cytokine production. These data suggest that FR delays the onset of autoimmune kidney disease by suppressing both Th-1 and Th-2 cytokine production.