Effects of vitamin E (E) supplementation on influenza infection were examined in young and old C57BL/6NIA mice fed 30 or 500 ppm of E for 6 weeks and subsequently infected with influenza A/Port Chalmers/1/73 (H3N2). Old mice fed 30 ppm of E had significantly higher lung virus titers on days 2 and 7 after infection than young mice fed 30 ppm of E. Titers on all 3 days were significantly lower in old mice fed 500 ppm of E than in those fed 30 ppm. Significant effects of E on lung virus titers in young mice were observed on only day 5, but E caused more reduction of virus titers in old than in young mice (25-fold vs. 15-fold). An age-associated decline in NK cell activity was restored by 500 ppm of E in old but not young mice. Pulmonary cytotoxic T lymphocyte activity on day 7 was not affected by age or E. These experiments demonstrate that high doses of E significantly enhance influenza viral clearance in aged mice but only modestly affect young mice.