The activities of the protective enzymes, superoxide dismutase, catalase and glutathione peroxidase have been measured in the cortical and nuclear sections of 76 human cataractous lenses as well as in calf, rabbit and rat lenses. No changes was observed in the activity of catalase with the progressive development of cataract. However, a precipitous decrease (70%) in both superoxide dismutase and glutathione peroxidase in the nuclear region of the lens was found at the onset of nuclear cataract. Further decreases accompanied the progression of the cataract and similar, but less marked, decreases were observed in the cortical region of the lens. It is suggested that the inactivation of these enzymes may result in an elevation of the H2O2 and O2.- levels in the lens and that this may be responsible for the oxidative modification of lens proteins observed in nuclear cataracts.