The main purpose of this study was to determine whether experimental enhancement of oxidative stress by exposure to hyperoxia is an appropriate model for the acceleration of the normal aging process or for establishing a causal association between oxidative stress and aging. Insect tissues are directly exposed to ambient air via the tracheolar invaginations and are thus highly susceptible to oxidative stress under hyperoxic conditions. Amounts of glutathione (GSH), glutathione disulfide (GSSG) and protein mixed disulfides (PrSSG) were compared under normoxic and 100% ambient oxygen in males of two different strains of Drosophila melanogaster (Oregon R (WT) and y w strains). The reason for using two different strains was to preclude the effects of genetic background and to determine whether variations in longevity of the two strains are associated with resistance to oxidative stress. Amounts of GSSG and PrSSG increased, whereas GSH:GSSG ratios declined as a function of age in both strains. Under hyperoxia, y w flies did not exhibit an increase in GSSG amount or a decline in GSH:GSSG ratio, whereas WT flies showed a decline in GSH:GSSG ratio only during the later part of hyperoxic exposure. In neither strain there was a progressive increase in PrSSG amount under hyperoxia. Results indicate that hyperoxia (100% oxygen) neither reproduces nor accelerates the pattern of alterations in glutathione redox state and PrSSG content observed during aging under normoxic conditions, although some other indicators of oxidative stress may be affected.