The present study investigates the mechanism underlying the alterations in sodium, potassium, and water content brought about by demecarium bromide and echothiophate iodide in the rabbit lens. Both agents cause a marked increase in lens permeability as measured by the leak-out of rubidium 86 from the lens. This altered permeability occurs prior to any gain in lens water and, in fact, is extant even when the lens is prevented from swelling by a hyperosmotic environment. Such data indicate that the change in lens permeability is a fundamental effect of the drug and not a secondary phenomenon resulting from lens swelling with attendant distortion of membranes. Under similar conditions cation transport, as judged by the ability of the lens to actively accumulate rubidium 86, remains normal. Demecarium interferes with the aerobic phase of glucose metabolism, shifting the economy of the lens exclusively to anaerobic pathways. In contrast, echothiophate appears to have no effect on lens metabolism.