Vitamin E homeostasis in hyperlipidemia is poorly understood. The biokinetics of deuterated alpha-tocopherol (alpha-T) in blood components was investigated in normolipidemic (N; total cholesterol < 5.5 mmol/L and triglycerides < 1.5 mmol/L, n = 9), hypercholesterolemic (HC; total cholesterol > 6.5 mmol/L and triglycerides < 1.5 mmol/L, n = 10), and combined hypercholesterolemic and hypertriglyceridemic (HCT; total cholesterol > 6.5 mmol/L and triglycerides > 2.5 mmol/L, n = 6) subjects. Subjects ingested 150 mg hexadeuterated RRR-alpha-tocopheryl acetate, and blood was collected up to 48 h after ingestion. Labeled alpha-T was measured in plasma, lipoproteins, erythrocytes, platelets, and lymphocytes by liquid chromatography/mass spectroscopy. In plasma, HC had an earlier time of maximum concentration (6 h) compared with N and HCT (12 h) (P < 0.05). HCT had a lower uptake of labeled alpha-T (P < 0.005) and a longer half-life (P < 0.05). In chylomicrons, the maximum labeled alpha-T concentration was higher in HC compared with N and HCT (P < 0.00005); however, HCT had a lower uptake of labeled alpha-T in LDL. In all groups, the lowest density LDL subfraction contained more labeled alpha-T than denser subfractions (P < 0.05). In platelets, lymphocytes, and erythrocytes, the areas under the labeled alpha-T concentration vs. time curves were in the order N > HC > HCT. In lymphocytes, differences in labeled alpha-T were found at 6 and 48 h (P < 0.05). These data demonstrate that there are differences in the uptake of newly absorbed alpha-T into blood components in hyperlipidemia. Because these blood components are functionally affected by vitamin E, reduced uptake of alpha-T may be relevant to the pathogenesis of atherosclerosis.