A conformational model of monovalent cation transport in mitochondria is described. Because it incorporates the proton-generated membrane potential and pH differential of the chemiosmotic model, the model successfully rationalizes a wide variety of mitochondrial ion-transport phenomena.The active transport of alkali metal cations in the mitochondrion can be greatly enhanced by exogenous ionophores. Thus the very same reagents that facilitate the passive transport of alkali metal cations through biological membranes and lipid bilayers also enhance their active transport. This strongly suggests that the same mechanism of permeation applies under both active and passive transport conditions.There are two types of ionophores, the neutral and the monocarboxylate or anionic ionophores (1, 2), and it has now been demonstrated that both types induce a form of active transport across the inner mitochondrial membrane (3, 4). The two types of ionophore induce two distinct types of active transport, each with its particular characteristics.Montal et al. (4) We have recently proposed a model of active transport that rests upon two fundamental assumptions: (i) there is a cycle of conformational change in the transduction of chemical free energy into the free energy of an ion gradient, and (ii) the physicochemical properties of the ionophores require that the movement of ions be spontaneously down local electrochemical potential gradients (6). However, the development of the model based on these two assumptions was very inadequate. The most obvious inadequacy was that it required the completely untenable binding of a large number of weak acid anions on the inner surface of the inner mitochondrial membrane. Furthermore, it did not involve in any intrinsic manner a cyclical conformational change, despite the fact that a cycle of conformational change was one of the basic postulates.