To evaluate the effect of dietary fat-induced alterations in triglyceride (TG) metabolism on plasma and very low-density lipoprotein (VLDL)-alpha-tocopherol, nine healthy males (mean +/- SEM, age: 36 +/- 3 years, BMI: 24.7 +/- 1.1) consumed a 35%-fat diet (control) for one week followed by a 15% low-fat, high-carbohydrate diet for 5 weeks. After each dietary phase, the subjects ingested an evening meal along with a 50 mg capsule of (2)H(6)-RRR-alpha-tocopheryl acetate; blood samples were drawn over a 24 h period while the subjects remained fasted. Low-fat feeding increased fasting plasma TG concentrations by 53% (116 +/- 27 to 178 +/- 32, mg/dl, p < 0.0001) primarily by reducing VLDL-TG clearance. Total plasma alpha-tocopherol concentrations (labeled + unlabeled) were unchanged (25.8 +/- 2.3 vs. 26.4 +/- 3.0 nmol/ml plasma) and no differences between the diets were observed for plasma (2)H(6)-alpha-tocopherol concentration (4.8 +/- 0.6 nmol/ml, for both diets) or enrichments (18.1 +/- 1.8% average for both diets). However, low-fat feeding significantly increased the amount of alpha-tocopherol in the VLDL fraction (43%, p = 0.04) in concert with elevations in VLDL-apoB and TG. The alpha-tocopherol and TG content of VLDL varied in parallel in individual subjects and fractional replacement rates and clearance of alpha-tocopherol and TG in VLDL were closely correlated. Kinetic parameters were decreased by 32-39% from high-fat to low-fat. These data suggest that vitamin E bioavailability is similar between a 15 and 35% fat diet, with a redistribution of alpha-tocopherol in lipoproteins occurring during low-fat feeding (increased in the VLDL fraction, reduced in the other lipoproteins), and transfer of alpha-tocopherol from VLDL depends upon TG removal from the particle, consistent with previous observations in vitro and in animal studies.