The use of multivariate spectrophotometric calibration for the simultaneous analysis of synthetic samples and commercial tablet preparations containing hydrochlorothiazide (HCT) and amiloride hydrochloride (AMH) is reported. Partial least squares (PLS-1) analysis of electronic absorption spectral data allowed the rapid and accurate resolution of mixtures in which the analyte ratios were approximately 10:1, without the need of a previous separation step and without interference from other sample constituents. The method, validated by the analysis of synthetic mixtures of both drugs, where accuracy over the linear working range as well as inter- and intra-assay precision were determined, was used in the concentration ranges of 21.7-30.4 mg l(-1) for HCT and 1.8-3.0 mg l(-1) for AMH. The proposed method was successfully applied to the evaluation of the stability of the stock solutions of the analytes in MeOH-H(2)O and to the elaboration of drug dissolution profiles of commercial tablets, results being concordant with those furnished by the USP technique. The method was also employed for the determination of drug content in two different pharmaceutical formulations, providing results that were in excellent agreement with those obtained by HPLC.