We investigated the pathophysiological significance in biomembranes of the redox dynamics of Vitamin E (alpha-tocopherol) which is lipophilic radical scavenger related to aging or pathologic status such as non-insulin-dependent diabetes mellitus or primary hyperlipidemia. Vitamin E eliminates lipid peroxyl radicals by the peroxidation chain reaction of the membrane lipid, and it becomes Vitamin E radical. Furthermore, the Vitamin E radical becomes Vitamin E quinone which is an oxidic metabolite of Vitamin E. Therefore, it was needed to determine the alpha-tocopherol and alpha-tocopherolquinone simultaneously to evaluate the antioxidative status of alpha-tocopherol in biomembranes exactly. For this purpose, we developed the assay method for the simultaneous determination of the two substances using HPLC system. Then we applied this method to basic and clinical research. 1) For the simultaneous determination of alpha-tocopherol and alpha-tocopherolquinone, highly-sensitive measurement system by HPLC-multiple coulometric ECD was developed. This system is useful to estimate the redox dynamics of alpha-tocopherol in biomembranes. 2) The utilization rate of alpha-tocopherol in the erythrocyte membrane of 10- to 120-week-old rats was significantly increased, whereas alpha-tocopherol uptake in the erythrocyte membrane decreased age-dependently. Furthermore, a significant increase in lipid hydroperoxide content and a marked decrease in the fluidity of the erythrocyte membrane were seen with age. 3) There was a strongly significant positive correlation between age and the utilization rate of alpha-tocopherol in the erythrocyte membrane of healthy volunteers aged between 23 and 103. 4) The alpha-tocopherol uptake in erythrocyte membrane was significantly lower in elderly non-insulin-dependent diabetes mellitus patients (average 68.1 years old) than in healthy subjects (average 71.8 years old). 5) The utilization rate of alpha-tocopherol in erythrocyte membrane and the alpha-tocopherol uptake in erythrocyte membrane were significant lower in elderly patients with primary hyperlipidemia (average 74.1 years old) compared to healthy subjects (average 71.2 years old). These findings suggest that the redox dynamics of alpha-tocopherol in biomembranes should be investigated with special regard to the onset, aggravation and complications of several diseases or aging as a result of oxidative stress. In addition redox dynamics were suggested to be useful to evaluate the grade of aging.