Characteristics of sodium ion-selective electrodes (Na-ISEs) with polymeric membranes incorporating cyclic and acyclic compounds as ionophores were studied and their applicability to analysis of physiological fluids was examined. In this study, bis[(12-crown-4)methyl] methyl(dodecyl)malonate [bis(12-crown-4)] and polyether-amide compounds (ETH 157, ETH 2120) were used as ionophores and adipic esters [bis(2-ethylhexyl) adipate, bis(1-butylpentyl) adipate] were used as plasticizers. These Na-ISEs showed Nernstian slope of 54 approximately 57 mV/decade and response time of < 10 s. Among three ionophores examined, bis(12-crown-4) was the most selective to Na+ in the presence of drugs [1, 1-dimethyl-5-methoxy-3-(di-2-thienylmethylene)piperidinium bromide monohydrate and [2-(alpha, alpha-dicyclopentyl acetoxy)ethyl] triethylammonium bromide] and lipophilic quaternary ammonium salts such as a cationic surfactant (trimethyloctadecylammonium salt) as well as cations. The cause of interference to three Na-ISEs by the above two drugs was studied. Then, the migration of interfering substances into the sensing membrane was suggested by the measurement of potential response characteristics. In the analysis of control serum samples, good reproducibility (C. V. = 0.3 approximately 0.4%) was obtained by all Na-ISEs. But accuracy in the analysis of patient serum samples was varied with the type of ionophore of Na-ISE. The deviation of error (S(yx) was as