High-performance liquid (HPLC) and gas--liquid chromatographic (GLC) methods for the measurement of the antidepressant nomifensine in human serum were developed and compared for precision, accuracy, sensitivity and convenience. No significant difference was found between these two techniques with regard to sensitivity and precision. Both methods can accurately measure serum nomifensine concentrations down to 8 nmol/1. The coefficient of variation (C.V.) for intra-assay variability of nomifensine was 4.8% (HPLC) and 5.5% (GLC) at 150 nmol/1. The HPLC method proved to be both simpler and more selective than the GLC method. The calibration graph was linear over the range 8-1000 nmol/1 in the HPLC method, but only up to 150 nmol/1 in the GLC method. The selectivity and simplicity of the HPLC method make it useful for both pharmacokinetic studies and therapeutic serum level monitoring of nomifensine. The HPLC method was applied to the analysis of serum samples obtained from four healthy individuals receiving therapeutic dosages of nomifensine.