Following administration of high levels of vitamin E, plasma tocopherol levels in mature humans and monkeys continued to increase with time. In man plasma tocopherol levels were higher when tocopherol rather than tocopheryl acetate was given. Mature female rats that had been maintained on laboratory chow were put on the diet supplemented with either 1,000 or 10,000 mg/kg of all-rac-alpha-tocopheryl acetate. All tissues analyzed (plasma, platelets, liver, red blood cells, adipose tissue, heart, lung, skeletal muscle, and brain) continued to increase in tocopherol content for the duration of the supplement (20 weeks). It was concluded that it is difficult to saturate tissue with tocopherol and that not only the level, but the duration, of supplementation with vitamin E influences the concentration of vitamin E in all tissues. Liver and adipose tissue both accumulated tocopherol at a very rapid rate compared to other tissues, but once the chow diet was resumed, liver tocopherol decreased very rapidly and adipose tissue decreased very slowly. The studies suggest that at least for a short time period, the liver is the major available storage organ for tocopherol. When animals were put back on the unsupplemented chow diet, platelet and plasma levels returned to baseline values within 1 week, and red blood cells, heart, muscle, lung, and brain within 4 weeks.