A rapid and specific method has been developed for the determination of orphenadrine concentration in plasma. It involves a one-step sample preparation using n-hexane/isopropyl alcohol (98:2) extraction, and analysis by gas chromatography on a wide bore capillary column using nitrogen/phosphorus detection. This procedure considerably simplifies previously reported assays and is specific and sensitive enough for the determination of orphenadrine in plasma of patients on chronic therapy.