A high performance liquid chromatographic method for the simultaneous quantitation of clozapinea member of the dibenzodiazepine class of antipsychotic drugsand its reduced metabolite in human plasma has been developed. Clozapine andN-desmethylclozapine are concentrated from blood samples by liquid-liquid extraction, followed by reverse-phase liquid chromatography. Accuracy of the determination is ensured by application of an internal standard, protriptyline, which is closely related to clozapine. A detection limit of 15 ng/mL for clozapine and 30 ng/ml forN-desmethylclozapine was achieved.