Sodium gradient-dependent 45Ca2+transport occurred across the lens membrane both in the direction of Ca2+uptake by inside-out vesicles and Ca2+efflux after Ca2+loading of right-side-out vesicles. Using the calcium ionophore, A23187,>90% of the Na+gradient-dependent Ca2+uptake was estimated to be free Ca2+. A normal Na+gradient was also required to maintain calcium homeostasis in the intact lens. The Na+gradient contributed to Ca2+efflux from lenses pre-loaded in medium containing 15 raM CaCl2. Therefore, a Na/Ca-exchange functions to control Ca efflux in rat lens, in addition to the Ca-ATPase. In the preweanling rat mature nuclear cataracts occurred by 96 h after subcutaneous injection of sodium selenite (30 nmol/g animal wt). A 3-5 fold increase of Ca2+acccompanied cataract formation. The loss of Ca2+homeostasis can be detected by 48 h after treatment selenite treatment. At this time the initial rate of Na+gradient-dependent Ca2+uptake was 30% lower in lens vesicles from selenite-treated rats compared to controls. No significant reduction of Na+,K+-ATPase activity was detected. Altered Na/Ca-exchange may contribute directly to the loss of Ca2+homeostasis that leads to nuclear cataract.