The uptake of alpha-tocopherol from 2R,4'R,8'R-alpha-tocopherol and 2R, 4'R, 8'R-alpha-tocopheryl acetate has been compared in rats and humans. The two forms of vitamin E were compared simultaneously in each subject (rat and human) by using a combination of deuterium-substitution and gas chromatography-mass spectrometry (GC-MS) to distinguish and measure the competitive uptake of alpha-tocopherol from an orally ingested mixture of the acetate and the free phenol forms. When rats were dosed in a manner analogous to that used in traditional bioassays, i.e., providing the two forms of vitamin E once daily in tocopherol-stripped corn oil for four successive days immediately prior to sacrifice, the net uptake of alpha-tocopherol from the free phenol form was only half that from the acetate. This result is consistent with the greater activity of the acetate that had been observed previously in bioassays. However, when the two forms of tocopherol were intubated into rats as a single dose mixed in with an aqueous bolus of standard laboratory diet, the amount of alpha-tocopherol taken up from the free form after 24 hr was very similar to that derived from the acetate. In five adult humans, competitive uptake studies of the two forms after a single dose taken with a meal showed that the amount of alpha-tocopherol from the free phenol form was equal to that from the acetate in plasma and red blood cells.(ABSTRACT TRUNCATED AT 250 WORDS)