Vitamin E is a potent, naturally occurring, lipid-soluble antioxidant, which is reported to be protective against several disease processes, including coronary atherosclerosis. We have measured the alpha-tocopherol content of the aorta, liver, skeletal muscle, and kidney of rats fed one of the following diets for 10 weeks: a normal control chow diet (i); or the same diet containing 1% cholesterol (ii); 0.5% vitamin E (iii); or 1% cholesterol plus 0.5% vitamin E (iv). The alpha-tocopherol content of serum and tissue extracts was measured by HPLC using gamma-tocopherol as an internal standard. Tissue and serum cholesterol content was measured using a cholesterol oxidase enzyme reagent kit. In all animals receiving the 1% cholesterol diet, serum cholesterol levels increased significantly (P < 0.005). By the 10th week, mean serum alpha-tocopherol levels rose significantly in both groups of animals receiving dietary vitamin E supplements (P < 0.0001) compared with their respective control group. This was accompanied by a significant increase in the absolute alpha-tocopherol content of liver (8- to 9-fold) and aorta (3- to 4-fold). The alpha-tocopherol content of renal and skeletal muscle tissue was raised 1- to 2-fold in both groups of rats on vitamin E supplements, however the increased attained significance only for the renal tissue. The aortic tissue alpha-tocopherol/cholesterol ratio was 4-fold higher in the rats receiving concomitant 1% cholesterol plus 0.5% vitamin E compared with animals receiving 1% cholesterol alone (P < 0.02), and was 5-fold higher in the rats receiving 0.5% vitamin E compared with those receiving control chow (P < 0.01). These data suggest that dietary vitamin E supplementation results in a differential uptake of alpha-tocopherol, which may be dependent, in part, on selective lipoprotein particle accumulation.