A liquid-chromatographic reversed-phase method employing a C18 column has been developed for simultaneous analysis of rifampicin, isoniazid and pyrazinamide in 0.1 M hydrochloric acid dissolution medium and in simulated gastric fluid. Good separations were achieved by employing a gradient prepared from methanol and 0.01M sodium dihydrogen orthophosphate buffer containing 0.05% w/v tetramethylammonium chloride (pH adjusted to 3.5). The detection wavelength was 254 nm. The method was validated for linearity, accuracy, precision and ruggedness. It was found to work well for analysis of the three drugs in the presence of degradation products and even for samples containing ethambutol, which does not interfere because of lack of UV absorption.