We studied the effects of feeding an antioxidant blend of vitamins, minerals and carotenoids to a mixed adult dog population (n = 40, mean 4.4 +/- 1.85 y) for a 16-wk period. Compared to the control group of dogs (n = 20), the antioxidant (AOX)-supplemented group of dogs (n = 20) demonstrated significant increases in plasma levels of vitamin E and taurine by 4 wk of supplementation (P < 0.01) and total antioxidant activity (as measured by ferric-reducing antioxidant power assay) by 8 wk of supplementation (P < 0.05). Following 8 wk of supplementation, the AOX-supplemented dogs also showed significant reductions in both endogenous and exogenous DNA damage (P < 0.005) compared to that of the control dogs, as measured by the comet assay. Over an 8-wk rabies vaccination course that started at 8 wk supplementation, the AOX-supplemented dogs also demonstrated significantly higher vaccine-specific virus-neutralizing antibody levels at 2, 4 and 6 wk postvaccination (P < 0.05) and a tendency toward establishing a vaccine-specific antibody response quicker than did the control group of dogs. These findings in dogs suggest that antioxidant supplementation can achieve sustained increases in circulating levels of antioxidants that exert a protective effect by a decrease in DNA damage, leading to improved immunological performance. These findings also have implications in a wider context where free-radical damage has been associated with a variety of degenerative disorders and the aging process in general.