The voltammetric behavior of antipsychotic drugs, such as, chlorpromazine hydrochloride and promethazine hydrochloride has been investigated at a glassy carbon electrode in Britton-Robinson buffer of pH 9, It was found by applying the differential pulse stripping voltammetry (DPSV) that both chlorpromazine hydrochloride and promethazine hydrochloride had well formed oxidation voltammetric waves, with the peak potential for chlorpromazine hydrochloride at 620 mV, and for the two peaks of promethazine hydrochloride at 444 and 668 mV. The calibrations were linear for chlorpromazine hydrochloride and promethazine hydrochloride in the concentration ranges of 0.05-1.2 and 0.1-1 mg 1(-1), respectively. However, the voltammetric peaks of these two drugs, seriously overlap and it is difficult to determine them individually from a response of a drug mixture. In this work, a method for the simultaneous determination of these two drugs is proposed, and is based on their oxidation at the glassy carbon electrode. The interpretation of the complex voltammograms is achieved with the aid of chemometric methods, such as, classical least squares (CLS), principal component regression (PCR) and partial least squares (PLS). The proposed method was applied to determine these two drugs in a set of synthetic mixtures and blood samples, and in general, satisfactory results were obtained, (C) 2001 Elsevier Science B.V. All rights reserved.