The discrimination between the natural form of vitamin E, RRR-alpha-tocopherol, and the synthetic form all-rac-alpha-tocopherol was measured in two experiments for plasma and tissues of rats. In Experiment A, the animals were fed RRR-alpha- or all-rac-alpha-tocopheryl acetate at two different levels, 0.035 and 0.200 g/kg diet, for 2.5 mo. In Experiment B, rats were first depleted of vitamin E for 7 wk then fed a diet containing 0.035 g/kg diet of RRR-alpha- or all-rac-alpha-tocopheryl acetate. In the latter experiment, rats were killed after 3, 7, 17, 31 or 45 d to study the time course of the discrimination. At the end of both experiments, levels of alpha-tocopherol were measured in plasma and tissues. The results showed a preferential uptake of the natural RRR-alpha-tocopherol by the majority of the tissues. The preference is small and in some tissues is not immediately manifested. The greatest discrimination in the tissues examined was found in red blood cells; the levels of alpha-tocopherol accumulated with the RRR-alpha-tocopherol diet were four to six times that accumulated with all-rac-alpha-tocopherol diet. For all other tissues, this ratio was between 1.0 and 1.5. These results indicate that tissues have a mechanism for alpha-tocopherol uptake, but this mechanism is not entirely specific for RRR-alpha-tocopherol.