A novel ion selective electrode is fabricated for naltrexone HCl and used in pharmaceutical analysis and drug determination inbiological fluids without complicated pretreatments and extractions, using direct potentiometry. The naltrexone complex with sodiumtetraphenyl borate (NaTPB) is obtained by in situ soaking PVC membrane electrode in an 1 × 10-3 M naltrexone solution. The sensorexhibited fast, reproducible and linear sub-Nernstian response over concentration range of 1 × 10-5 - 1 × 10-3 M with a detection limit of5 × 10-6 M. The membrane sensor was successfully applied to the determination of naltrexone in capsules as well as for its determinationin urine and plasma samples.