Two high-performance liquid chromatographic methods for monitoring haloperidol (HAL) and reduced haloperidol (RHAL) plasma concentrations were compared. In one method ultraviolet detection and a C18 column were used (UV method); in the other method electrochemical detection and a CN-column were used (EC method). Both methods are accurate and precise. For plasma samples spiked with HAL or RHAL, an excellent correlation was observed between the concentrations of HAL and RHAL found with both methods(r ≤ 0.99, p < 0.01). However, for plasma obtained from patients treated with HAL the correlation between the two methods was poor (r ≥ 0.71, p < 0.01). The main reason for the discrepancy between the two methods is probably interference of comedications or their metabolites, mostly in the EC method. Although the quantitation limit of the UV method (2 ng/ml for HAL and RHAL) is higher than that of the EC method (0.5 ng/ml for HAL and RHAL), the UV method is to be preferred for monitoring plasma levels in psychiatric patients because there is less interference from comedication.