A new method, using high-performance liquid chromatography/ion electrospray (negative ion) mass spectrometry, has been developed for the determination of a hydrophilic liver-specific inhibitor of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase, pravastatin in human plasma. In this method, plasma samples were prepared by a solid-phase extraction on C(18) Bond Elut cartridge. Chromatography was carried out with a Zorbax C(8) column. Simple isocratic chromatography conditions were used. The method has been validated in a linear range of 0.25-300 ng/ml with a coefficient of variation of 0.6-3.4%. The overall recovery was 90.5% for pravastatin and 90.8% for the internal standard beta-hydroxy-lovastatin. The method is simple and reliable with a total run time of less than 2 min.