Different types of PVC-matrix ion-selective electrodes (ISEs) that respond to the cationic form of diphenhydramine (Dph) are described. Three ion-pairing agents, namely tetraphenylborate (TPB), phosphotungstate (PT), reineckate (RN) are investigated. The best PVC polymeric membrane contains Dph-TPB as active material. The electrode, based on the ion-pair complex with TPB anion shows near-Nemstian response in the concentration range 10(-2) to 3.5 x 10(-5) M (Dph.HCl). Changing pH within the range 2.0-7.5 did not affect the electrode performance. The standard electrode potentials were determined at different temperatures and used to calculate the isothermal coefficient of the electrode (0.00156 V/degrees C) The electrode showed a good selectivity for Dph with respect to a large number of inorganic and organic cations. The standard addition method and potentiometric titration were applied to determine Dph amounts in pharmaceutical preparations. The Dph selective membrane electrode was also applied to the determination of the dissolution profile of Dph tablets. The dissolution results were compared with spectrophotometrically determined ones.