The effect of adding surface-active agents to electrolytes containing isoniazid (INH), an antituberculous drug, on the voltammetric response of carbon paste electrode (CPE) was studied. The enhancement of current signal due to the oxidation process was a function of the amount of analyte, pH of the medium, surfactants' type, and chain length and aromaticity and accumulation time at the electrode surface. Eight surfactants were used, three anionic type, sodium dodecyl sulphate (SOS), sodium octyl sulphate (SOS) and sodium dodecyl benzene sulphonate (SDBS), three cationic type, cetyl trimethyl ammonium bromide (CTAB), trimethyl octyl ammonium bromide (TMOB) and cetyl pyridinium bromide (CPB) and two nonionic surfactants, albumin and Triton X-405. Addition of SOS and SDBS to the isoniazid-containing electrolyte was found to enhance the oxidation current signals while SOS showed an opposite effect. The addition of either the cationic or nonionic surfactants was found to decrease oxidation current signals. To confirm the interactions between surfactant and isoniazid, absorbance spectroscopy has been performed. NMR measurements gave a good expectation for the location and orientation of INH in different micelles and gave a similar conclusion to that obtained from electrochemical and UV-vis data. The use of SDS in the electrochemical determination of isoniazid using differential pulse voltammetry at carbon paste electrode improved the limit of detection to 6.29 ng mL(-1). The validity of using this method in the determination of drug active ingredient in tablet formulations was also demonstrated. (C) 2010 Elsevier Ltd. All rights reserved.