Most cells are capable of active transport of sodium and potassium across the cell membrane. The human red blood cell is one of the best studied systems with regard to the characteristics and mechanism of active cation transport. A membrane-associated enzyme, adenosine triphosphatase activated by Na and K (Na,K-ATPase), appears to be identical with the Na-K pump. The evidence includes similar kinetic properties and responses to cardiac glycosides of the pump and Na,-K-ATPase, the spatial asymmetry of activation of both pump and enzyme by K and Na, and synthesis of ATP mediated by the pump working in reverse. The energy-dependent transfer of Na and K through the membrane appears to be associated with the following reactions of Na,-K-ATPase: Na-dependent phosphorylation of the enzyme; conversion to a second form of phosphorylated enzyme; and K-dependent release of phosphate.