Using isolated frog sartorius muscles, tracer experiments and chemical analysis for K+ and Na+ were performed to evaluate the mode that the removal of external K+ or Ca++ affects on the change in internal K concentration.1. During the continuous depolarization of the muscle membrane, K42 efflux was increased continuously while Ca45 efflux was increased transiently. Although the changes in K or Ca efflux showed a parallelism with the change in membrane potential it is reasonable to suppose that the vacancy of the Ca++ or K+ sites of the membrane due to the withdrawal of external Ca++ or K+ is the first step of the change in internal K under these conditions.2. The exchange between ions of the same species takes place, at the membrane, more preferentially than the interchange between an ion and ions of different species. The K+-K+ exchange in Ringer is not qualitatively different from the K+-Na+ interchange in K free Ringer, because these two processes are capable of translating from each other by the condition which is determined by the ionic composition on both sides of the membrane.3. By repetitive stimulation, Na increase within the muscle occurred at the cost of K release in Ringer. This efflux of K+ is different in nature from the net efflux of K+ in K free Ringer. Accordingly, the K ions movable outwards are the adjuster for maintaining the constancy of internal milieu.4. The influence of the removal of external K+ or Ca++ upon the internal K loss takes place by different means. Detail of each process has been interpreted by the change in the pattern of association/dissociation of K or Ca ions with/from the membrane anionic sites.5. Removal of external K or Ca ions first produces the change in the membrane molecular configuration. Then, external K+ influences upon internal K energetically through homogeneous K pool while Ca+ does informationally through heterogeneous pools of K, Ca or both.