Two methods are described for the determination of rifampicin and isoniazid in mixtures by visible spectrophotometry and first-derivative ultraviolet spectrophotometry. The absorbance at 475 nm in buffer solution pH 7.4 was employed to determine rifampicin after applying the three-point correction technique between 420 and 520 nm, while the amplitude of the first-derivative spectrophotometric spectrum at 257 nm in HCl 0.012 M was selected for the determination of isoniazid. The methods are rapid, simple and do not require any separation step. The recovery average was 99.03% for rifampicin and 100.01% for isoniazid. The methods were applied to determine the two compounds in commercial capsules and compared with the official method of the USP XXIII with good agreement between the results.