In summary, in vitro oxidation of lens crystallins mimics many of the post-translational modifications observed with age and in cataracts These results lend further support to earlier proposals that oxidation is a key factor in cataract formation. The extent to which ascorbate contributes to the oxidation reactions in vivo is not known. In addition to the data presented here that ascorbate can produce these effects in vitro, other observations support the possibility that under certain conditions ascorbate may be involved in the generation of reactive oxygen species in the lens. Using electron spin resonance the ascorbyl radical can be detected early in nuclear cataract formation, and there appears to be a decrease in total ascorbic acid (reduced and oxidized), suggesting further oxidation of ascorbate. Iron and copper are both present in mammalian lenses, and there are reports of increased copper levels in the lens with age and in cataracts. Increased metal ion concentrations would facilitate these oxidative processes.