Interactions of lanthanum and some local anesthetic drugs with divalent cation uptake have been studied in rat liver mitochondria. The oxidation-reduction changes of the respiratory chain components and the development of the membrane pH gradient were measured during ion uptake. The trivalent ion lanthanum was found to be a powerful inhibitor of divalent cation uptake with half-maximal effect observed at concentrations of approximately 0.1 mμmole La3+/mg protein. The neurotropic drugs butacaine, dibucaine, chlorpromazine, and phenergan enhanced remarkably the divalent cation-induced membrane pH gradient. The possible mechanism of the action of lanthanum and local anesthetics ou mitochondrial membranes is discussed. © 1968.