The effect of glucose on the insolubilization of lens proteins was investigated in the presence of visible light. The amount of glucose-induced insolubilization of lens proteins showed a dose-dependent increase. The velocity of insolubilization accelerated under acidic conditions. These results suggest that this phenomenon may be due to the direct action of glucose rather than glycosylation. 1H-NMR spectroscopy results suggest that the action of glucose might be to induce conformational changes, and aggregation of the proteins. The in vitro observation of glucose-derived insolubilization of the lens proteins may be similar to that observed in diabetic mellitus. Elevated free glucose per se may have a role in diabetic cataractogenesis in addition to the metabolism of glucose to sorbitol and osmotic changes to the lens. Protein structural perturbation by glucose was demonstrated with isolated proteins from the aged normal human lenses over 40 years and may contribute to senile cataractogenesis. The results suggest that elevated lens glucose may act directly as one of the triggers of cataractogenesis.