The cell surface membrane comprises an insulating lipid bilayer in which specialised proteins are embedded. This supports the membrane potential difference between intracellular and extracellular fluids brought about by their differing Na+, K+ and Cl- concentrations, their respective Nernst potentials for electrochemical equilibrium, and their relative membrane permeabilities. The concentration distributions arise from metabolically dependent active ion transport through membrane Na+-K+ ATPase activity, first demonstrated using radioactive tracers in cephalopod giant axons. In intact cells, these factors are combined with the Donnan distribution properties for intracellular and extracellular ions, reflecting the presence of impermeant intracellular charged protein, to determine the resting potential. The intact cell thereby forms an osmotically and electrically balanced system with relatively increased intracellular K+ and extracellular Na+ concentrations separated by a membrane across which there is a stable negative resting potential. The latter provides the electrophysiological background upon which cell excitation events are superimposed.