Lens crystallin glycation, thiol oxidation and aggregation showed parallel changes in streptozotocin-diabetic and aging rats. The levels of the disulfide-linked HMW aggregates were essentially the same in the diabetic and senile cataracts, but glycation was significantly lower in the latter. Inhibition of glycation by acetylating potential glycation sites by aspirin during in vitro glycation and in diabetic rats has led to inhibition of protein thiol oxidation and aggregation. A predominance of glycated crystallins, gamma crystallin in particular, was noticed in the HMW aggregates. Likewise, the glycate portion of the whole crystallin preparation showed an enrichment of the HMW aggregates. These observations strongly suggest a significant contribution by crystallin glycation in the formation of disulfide-linked aggregates.