A differential pulse polarography (DPP) for the simultaneous determination of isoniazid and rifampicin was proposed. Under optimum experimental conditions (pH = 7, scan rate = 10 mV/s, pulse amplitude = -50 mV), serious overlapping polarographic peaks were observed in the mixture of these compounds. In this study, support vector regression (SVR) was applied to modeling the overlapped polarograms. Furthermore, a comparison was made between the performance of SVR and partial least square (PLS) on data set. The experimental calibration matrix was designed with 30 mixtures of these compounds. Calibration graphs were linear in the range of 6 x 10(-8)-10(-4) and 10(-7)-10(-4) M for isoniazid and rifampicin. respectively. The results demonstrated that SVR is a good well-performing alternative for the analysis and modeling of DPP data than the commonly applied PLS technique. (C) 2010 Elsevier Ltd. All rights reserved.