Clinical surveys suggest that miotics produce lens opacities. Since such studies examine the diseased eyes of an older age group, interpretation is often difficult. The current study investigates the direct effect of miotics on the isolated rabbit lens in tissue culture. Both demecarium bromide (Humorsol) and echothiophate iodide (Phospholine Iodide) bring about subcapsular vacuoles, though their topographical distribution is different in the case of each drug. Both miotics alter cation and water balance in the lens, causing an increased sodium, decreased potassium, and gain in lens water. The rapidity of onset and the severity of these lesions exhibit a dose dependency. Although a cholinesterase is present at the lens surface, inhibition of the enzyme appears to have no direct role in the pathogenesis of the drug-induced cataract. The meaning of these studies in regard to the clinical situation is uncertain.