This chapter discusses the effects of potassium (K) deficiency on Na, K homeostasis and Na+, K+-ATpase in muscle. The exposure of cells to a low extracellular K concentration in vitro leads to a progressive loss of intracellular K associated with a gain of Na. The maintenance of constant intracellular Na, K contents depends on, among other things, the activity and the concentration of Na+, K+-ATPase in the plasma membrane. An increase in the intracellular Na/K concentration ratio will lead to an activation of the Na,K pump, possibly allowixg the establishment and maintenance of a new steady state. The detection of quantitative changes in the total Na+, K+-ATPase activity of muscle cells is difficult for three major reasons: the presence of several other ATPases gives rise to a considerable background activity; attempts to purify the Na+, K +-ATPase usually only allow the recovery of a few percent of the initial activity, leaving considerable uncertainty about the total quantity of enzyme; and the formation of inside-out vesicles or other structural changes during the preparation procedures may imply that the final purified material used for quantitative evaluation is not representative.