A precise and sensitive method is described for the determination of the antidepressant drug tranylcypromine in human plasma and urine using high-resolution gas chromatography. The drug, together with an added internal standard, is extracted from the plasma or urine sample, derivatized with heptafluorobutyric anhydride and analysed on an OV-225 support-coated open-tubular glass capillary column with nitrogen-sensitive detection. The method has been applied to the measurement of tranylcypromine levels in plasma and urine from both healthy volunteers and from psychiatric patients receiving a therapeutic dosage of the drug.