A high glucose concentration in vivo or an increased glucose of glucose 6-phosphate concentration in vitro has been found to lead to the glycosylation of epsilon-amino groups of lysine residues in bovine and rat lens crystallins. In vitro, this glycosylation imparts an increased susceptibility of the crystallins to sulfhydryl oxidation. Disulfide crosslinks result in the formation of high molecular weight aggregates and an opalescence in the crystallin solutions. The addition of reducing agents prevents as well as reverses the formation of high molecular weight aggregates and the opalescence of the crystallins. These phenomena suggest a new interpretation of previous results on cataract formation and a new approach for development of drugs to prevent cataracts.