A chloride-selective solvent polymeric membrane electrode based on a neutral hydrogen bond forming ionophore, poly(vinyl chloride) (PVC), the plasticizer 2-nitrophenyl octyl ether (o-NPOE), and cationic sites (50 mol %, relative to the ionophore) is described. At pH 7.0 (HEPES buffer), this electrode responds to chloride in a linear range from 10-5 to 10-2 M with a slope of (-54.0 ± 1.0) mV/decade and a detection limit of (6.5 ± 3.0) × 10-6 M. As compared to conventional anion-exchanger electrodes, the interference of SCN-, Br-, NO3 -, I-, and even salicylate is considerably reduced, as shown by the selectivity coefficients determined with the matched potential method (MPM) in the chloride concentration range 10-2.34-10-2.04 M (log KClj pot (MPM): sal-, + 1.8; SCN-, +1.6; NO3 -, +0.7; I-, +0.5; Br-, +0.4). Because the discrimination of the more hydrophilic anions SO4 2-, HSO3 -/SO3 2-, OAc-, HCO3 -, and H2PO4 -/HPO4 2- is too large for a determination of accurate selectivity coefficients in this high chloride concentration range, corresponding values for the range 10-5.00-10-4.70 M Cl- have been determined (log KClj pot (MPM): SO4 2-, -1.2; HSO3 -/ SO3 2-, -2.0; OAc-, -2.3; HCO3 -, -2.6; H2PO4 -/ HPO4 2-, < -3.5), showing here, too, a good selectivity for Cl-. The chloride ion concentration in certified control horse serum was determined by the standard addition method as 102.1 mM with a coefficient of variation of 0.42% (n = 6), This result is in excellent agreement with the certified value of 102.3 mM, as determined by coulometry, and demonstrates the applicability of this sensor for measurements in biological samples. The selectivity upon storage of the electrode in buffer solution for 4 weeks decreases but is still considerably better than that for a freshly prepared anion-exchanger electrode.