The injection of glucocorticoids into the vitreous chamber of the rabbit eye results in the development of posterior subcapsular opacities. These lesions appear to be similar in morphology to human steroid-induced cataracts. Electron microscopic analysis revealed fiber cell separation, vacuolization, and changes within the matrix of the crystallins. Opacification could only be produced by glucocorticoids possessing a reactive C-20,21 hydroxylcarbonyl function, supporting the hypothesis that glucocorticoid addition products are involved in the induction of these lesions. The occurrence of glucocorticoid-lens proteins adducts was confirmed by tritium incorporation and by radioimmunoassay of protein hydrolysates obtained from these lenses.