A sensitive and selective high-performance liquid chromatographic (HPLC) method for the simultaneous quantitation of modafinil and its acid metabolite in human plasma has been developed. The method is based on a liquid-liquid extraction followed by isocratic reversed-phase HPLC with ultraviolet absorbance detection at 236 nm. The eluent used was acetonitrile-water-acetic acid (150:420:12, v/v/v). The run time was 45 in. The method provided a detection limit of 0.04 mg/l for modafinil and the acid metabolite, a quantitation limit of 0.13 mg/l for modafinil and 0.14 mg/l for the acid metabolite. A good linear relationship was obtained in the concentration range studied (0.1-20 mg/l) for both compounds and the method was sufficiently accurate and precise to support clinical pharmacokinetic studies. To our knowledge this is the first described method for determination of modafinil and its acid metabolite in plasma.