The mechanism of the Na+-independent Ca 2÷ eftlux system in mitochondria has not been elucidated as yet. With the aid of cyclosporin A, an inhibitor of the Ca2+-induced 'pore', and using a variety of inhibitors, uncouplers and ionophores, it is possible to demonstrate, unequivocally, that this process is driven by ApH. The efflux is not affected by A~u, thus suggesting an electroneutral CaZ+/2H ÷ exchange mechanism. Parallel measurements of the rate of Ca 2÷ efflux and 3pH, as modulated by valinomycin and nigericin, indicate that the rate of efflux is a function of the magnitude of ApH.Mitochondria; CaZ+; Ca2+/2H + exchange; 3pH; Cyclosporin A