Plasma and tissue alpha-tocopherol concentrations are remarkably stable, which suggests that they are regulated. alpha-Tocopherol transfer protein, tocopherol-associated protein, and tocopherol-binding protein bind alpha-tocopherol. These proteins might function as tocopherol regulatory proteins, although only tocopherol transfer protein has been shown to influence plasma and tissue alpha-tocopherol concentrations. Tissue alpha-tocopherol concentrations likely depend on tocopherol regulatory protein function and tissue lipid content, vitamin E uptake and efflux, oxidative stress, and interactions between vitamin E and other antioxidants. Pharmacokinetic models often divide tissues into rapidly perfused, slowly perfused, and very slowly perfused compartments. Tissue vitamin E concentrations might equilibrate more rapidly in tissues with greater perfusion, greater vitamin E uptake, increased amounts or activities of tocopherol regulatory protein, and lower lipid contents. The rate at which tissue concentrations approach equilibrium, however, does not predict the final equilibrium concentrations because of redistribution among tissues. Redistribution of vitamin E to adipose tissue from other tissues may be significant. Intracellular trafficking of vitamin E might occur in conjunction with membrane recycling because membrane constituents rapidly recycle between the plasma membrane and intracellular endocytic compartments. Thus, tocopherol regulatory proteins may modulate rather than directly regulate vitamin E tissue distribution and intracellular trafficking.