AbstractHuman lymphocytes were equilibrated for 48 hours over a wide range of external potassium levels, and their contents of potassium, sodium, and water determined. As external potassium rose from zero, cell potassium rose steeply in a sigmoidal fashion, reached half‐saturation at 0.4 mM external potassium, and then saturated at 129 mmoles/kg cells. The saturable cell potassium exchanged mole‐for‐mole with sodium. Analysis of the saturable components by a statistical‐mechanical adsorption model demonstrated a cooperative interaction between sites determining equilibrium potassium‐sodium distribution. Superimposed upon the saturable fraction of cell potassium was a smaller one that was non‐saturable with increasing external potassium to at least 64 mM, and that, when expressed as mmoles/liter cell water, existed in a ratio to external potassium of 0.6. The results strongly support the association‐induction hypothesis, which predicts a small non‐saturable component of ions determined by exclusion from oriented cell water and a cooperative interaction between sites throughout the cell that associate with pota