Aging is associated with reduced T cell function, as demonstrated by decreased T cell proliferation and IL-2 production. These changes respond to supplemental vitamin E both in animals and humans, in part by the reduction of T cell suppressive PGE(2), the production of which by macrophages is increased with age. To evaluate whether vitamin E has a direct PGE(2)-independent effect on T cell responses, T cells purified from the spleens of young and old mice were preincubated with vitamin E or vehicle control. Activation-induced cell division of T cells from old mice was lower than that by young, and the production of IL-2 following 48-h activation was less by T cells from old mice. There was an age-related decline in both the number of IL-2+ T cells and the amount of IL-2 produced per cell. Despite decreased IL-2 protein at 48 h, the expression of IL-2 mRNA at 6 h and IL-2 protein production at 6 and 16 h was greater by T cells from old mice compared with that of young. Age-related decline in cell division and IL-2 production at 48 h was only observed within the naive T cell subpopulation. Vitamin E increased both cell-dividing and IL-2-producing capacity of naive T cells from old mice, with no effect on memory T cells. These data indicate that naive T cells exhibit the greatest age-related defect and show for the first time that supplemental vitamin E has direct immunoenhancing effect on naive T cells from old mice.