In kidney cortex slices from rats and rabbits, cell K is known to be distributed between a diffusible compartment (Kd) and a nondiffusible pool (Knd). In the cold, Knd fails to exchange with extracellular Na or K despite the high permeability of the outer cell membrane to both Na and K. The Knd compartment is freely accessible only to metabolically linked K fluxes, whereas both active and passive fluxes occur into Kd. The distribution of K between Kd and Knd is altered by ouabain, cyanide, dinitrophenol, Ca, and other agents. This effect occurs in the absence of changes in the total K content of the cells and may represent an intracellular action of the drugs. The response of Knd to alterations in pH in vitro corresponds to the influence of acidosis or K deficiency in vivo. Together with the previous finding of a functional difference between Kd and Knd in vitro, the fact that the distribution of cellular potassium between two compartments can be altered by treatment of intact animals, as well as in slices, suggests that this potassium compartmentation may possess physiological significance.