This report reviews the use of ion-selective microelectrodes to measure intracellular ionic activities and ionic electrochemical potential differences across cell membranes. Particular emphasis is placed on the electrochemical characteristics of liquid ion-exchanger microelectrodes. Methods for assessing the effect of interfering ions on the electrode potential are discussed and analyzed. An equivalent electrical circuit model is proposed in which deviations from their theoretical values of the slopes and selectivities of liquid ion-exchanger microelectrodes are analyzed in terms of surface conductance phenomena. A quantitative expression is developed that permits the transmembrane electrochemical potential difference for an ion, which is measured with an ion-selective microelectrode, to be corrected for deviations from ideality in the slope of the electrode response. The effect of lipophilic anions, dissolved in the organic ion-exchanger solution, on the electrochemical characteristics of cation selective liquid ion-exchanger microelectrodes containing neutral ionophores is discussed.