Studies over the last two decades equating diet with chronic diseases have linked the highest consumption of mixed fruits and vegetables to a reduced risk of coronary heart disease (CHD), stroke, cataracts, and cancer at multiple sites. High levels of natural antioxidants, including the carotenoids, tocopherols, and ascorbic acid appear to be responsible for these reductions in risk. However, long-term intervention studies to alter chronic disease outcomes have generally used a single nutrient such as beta- carotene at high doses, and results have been disappointing. Because antioxidants have multiple and synergistic interactions and also enhibit compartmentalization and tissue specificity, it appears desirable to use supplementation that increases blood levels while simulating combinations of these chemoprotective substances in amounts more closely approximating amounts of mixed diets. This study measured carotenoid and tocopherol levels in human plasma after supplementation with dehydrated fruit and vegetable extracts (Juice Plus+®). Serum lipid peroxides were also measured to assess the effectiveness of supplementation in modifying oxidative processes. Fifteen healthy adults (10 women, 5 men; age range, 18 to 53 years) consumed supplements twice daily with meals for 28 days, with fasting plasma and serum samples taken at baseline and 7, 14, and 28 days. After 28 days, plasma antioxidant levels increased significantly: beta- carotene, 510%; alpha-carotene, 119%; lutein/zeaxanthin, 44%; lypocene, 2046%; and alpha-tocopherol, 57%. Serum lipod peroxides decreased fourfold after 7 days and remain significantly lower than baseline at 28 days (baseline, 16.85 ± 16.91 µmol/mL 28 days, 4.22 ± 3.78 µmol/mL). Decreases in lipid peroxide levels were coincident with increases in carotenoids and alpha-tocopherol, and reflect functionally improved oxidative defense mechanisms. Because these bioactive compounds can act synergistically, the effect cannot be attributed to any one component, but it may reflect a combined mechanism of antioxidant defense. Marked increases in plasma levels of predominant dietary carotenoids and alpha-tocopherol in all subjects indicate that supplementation with fruit and vegetable concentrates may prove effective in future intervention studies.