Changes in lens proteins induced at the early stages of cataractogenesis in cac (Nakano) mice were investigated by two-dimensional gel electrophoresis (2D-PAGE). The 2D-PAGE profile of lens proteins in 21-day-old cac mice differed from that in 27-day-old normal mice, even though the appearance of 'pin-head' nuclear opacity (26-day-old) had not yet been observed in the lenses. Especially noticeable were great differences in the polypeptides associated with the alpha- and beta- crystallin subfractions, the appearances of which corresponded to an increase in a ratio of the amounts of Na+ to that of K+ in the lenses of defective mice. No dramatic decrease in the gamma-crystallin fraction was observed until the mature cataract stage.