Oxidative stress is a component of diseases and degenerative processes associated with aging. However, no means are available to assess causative oxidative events separately from decline in function of protective antioxidant systems. Previous studies show that ongoing oxidative processes maintain plasma cysteine/cystine redox at a value that is more oxidized than the antioxidant glutathione/glutathione disulfide (GSH/GSSG) system, suggesting that redox analysis of these plasma thiols could allow separate evaluation of an increase in oxidative events from a decline in antioxidant function. The present study uses measurement of cysteine/cystine and GSH/GSSG redox in plasma of 122 healthy individuals aged 19-85 years to determine whether thiol-disulfide redox changes occur with age. The results show a linear oxidation of cysteine/cystine redox state with age at a rate of 0.16 mV/year over the entire age span. In contrast, GSH/GSSG redox was not oxidized prior to 45 years and subsequently was oxidized at a nearly linear rate of 0.7 mV/year. These data suggest that there is a continuous, linear increase in oxidative events throughout adult life but that the capacity of the GSH antioxidant system is maintained until 45 years and then declines rapidly. The data further suggest that redox states of cysteine/cystine and GSH/GSSG provide an approach to clinically distinguish between increased causative oxidative events and decreased GSH antioxidant function. In principle, such analyses can be used to assess efficacy of intervention strategies against oxidative stress prior to or early after onset of clinical symptoms in aging and age-related disease.