Isocratic reversed-phase high-performance liquid chromatography with coulometric electrochemical detection was optimised to quantify the neuroleptic drugs chloroprothixene, levomepromazine, and promethazine in human serum. The method involves extraction of the neuroleptic drugs in n-heptane-isoamylalcohol from the alkalinized serum, followed by chromatographic separation on a Nucleosil CN column with acetonitrile-pyridine-sodium acetate buffer as the mobile phase. The extraction recovery was > 85% for each neuroleptic drug. The sensitivity and selectivity required for pharmacokinetic studies was obtained with a dual coulometric analytical cell operating in the oxidative screen mode. The lower limit of detection in human serum for chlorprothixene, levomepromazine, and promethazine, was 0.5, 0.2 and 0.1 ng/ml, respectively. A linear relationship (r2 > 0.99) was obtained between the concentrations of each neuroleptic drug and the detector signal. The accuracy of the quality control samples was +/- 7% for each neuroleptic drug with a precision within 9.5%, 8.1% and 13.5% for chlorprothixene, levomepromazine, and promethazine, respectively. The neuroleptic drugs were stable in acetonitrile and human serum for at least six months when stored at -20 degrees C. This method is applicable to analyze a large number of serum samples for pharmacokinetic studies of the neuroleptic drugs.