This paper reports the role of glutathione (GSH) in the crystalline lens as an antioxidant against the oxidation of lens protein. GSH levels in normal lenses decreased gradually with increasing age, from approximately 5 mumol per g lens (wet weight) to 3 mumol per g lens (wet weight). On the other hand, levels of oxidized GSH in the lenses increased until the age of 40. After that, it remained almost constant at the level of approximately 0.9 mumol per g lens. Protein-bound GSH levels in both soluble and insoluble lens proteins dropped noticeably in the 50-year and older age groups, although there were significant differences in levels between both fractions. A decrease of tryptophan and tyrosine residues in lens proteins was proportional to a decrease in GSH levels in the lens as a result of aging. Those residue levels in the cataractous lenses were approximately half those in the normal lens proteins, and GSH levels in such lenses were almost one-tenth that in the normal lens. This study revealed that GSH may play an important role in preventing the oxidation of lens proteins from various oxidants. Furthermore, it is conceivable that these normal changes in GSH levels in the lenses increase the vulnerability of the lens to senile cataractogenesis.