Nickel electrodes chemically modified with an interfacial layer of nickel ferrocyanide are shown to be of analytical utility for simultaneously sensing sodium and potassium ions in aqueous solutions, human whole blood serum, and human whole blood. By controlling the charge-transfer characteristics of this versatile interface, interfering blood proteins and potential interferences associated with other alkali cations can be avoided. A solid-state model which explains the excellent simultaneous selectivity and sensitivity of the nickel ferricyanide interface is proposed.