Vitamin E and carotenoids are known to act as antioxidants both in vitro and in vivo. In this review we present a series of studies in healthy subjects and in patients who exhibit either acute or chronic oxidative stress. In the EU-Commission funded VITAGE project we investigated the status and effects of vitamin E and carotenoids on oxidative stress in 300 healthy volunteers. Depletion studies limiting dietary vitamin E or carotenoid intake to approximately 25% of the dietary reference intakes and subsequent repletion by supplementation with either large doses of vitamin E or intermediate doses of carotenoids showed significant changes in ex vivo LDL oxidizability, total plasma peroxide concentrations and urinary 8-oxo-7,8-dihydro-2(')-deoxyguanosine excretion. Patients on chronic hemodialysis present with oxidative stress in the presence of normal vitamin E but impaired vitamin C status and, due to anemia, need to be treated with parenteral iron. We studied the effects of a single oral dose of vitamin E taken 6 h prior to intravenous infusion of 100 mg iron, which exceeded the iron-binding capacity of transferrin. Vitamin E significantly reduced and in combination with a single dose of vitamin C completely abrogated acute oxidative stress induced by the iron load. Patients with cystic fibrosis are exposed to chronic oxidative stress due to an overproduction of reactive oxygen species as a result of neutrophil-dominated lung inflammation and impaired antioxidant status. Biochemical vitamin E and carotenoid deficiencies could be fully corrected even in the presence of fat malabsorption using intermediate doses of either RRR alpha-tocopherol or all-rac alpha-tocopheryl acetate and water-miscible all-trans beta-carotene. Long-term supplementation reduced ex vivo LDL oxidizability, in vivo lipid peroxidation and lung inflammation.