A simple and precise stability-indicating liquid chromatography method is developed and validated for the quantitative simultaneous estimation of irbesartan (IRB) and hydrochlorothiazide (HCTZ) in combined pharmaceutical dosage form. A chromatographic separation of the two drugs was achieved with an Ace5 C(18) 25-cm analytical column using buffer-acetonitrile (70:30 v/v). The buffer used in mobile phase contains 50 mM ammonium acetate pH adjusted 5.5 with acetic acid. The instrumental settings are flow rate of 1.5 mL/min, column temperature at 30 degrees C, and detector wavelength of 235 nm using a photodiode array detector. IRB, HCTZ, and their combination drug products were exposed to thermal, photolytic, hydrolytic, and oxidative stress conditions, and the stressed samples were analyzed by the proposed method. Peak homogeneity data of IRB and HCTZ is obtained using photodiode array detector. In the stressed sample chromatograms, it demonstrated the specificity of the assay method for their estimation in presence of degradation products. The described method shows excellent linearity over a range of 10-200 microg/mL for IRB and 5-100 microg/mL for HCTZ. Methylparaben was used as internal standard. The correlation coefficient for IRB and HCTZ are 0.998 and 0.999. The mean recovery values for IRB and HCTZ ranged from 100.45% to 101.25%. The limit of detection for IRB and HCTZ were 0.019 and 0.023 microg/mL, respectively, and the limit of quantification were 0.053 and 0.070 microg/mL, respectively. The proposed method was suitable for quantitative determination and stability study of IRB and HCTZ in pharmaceutical preparations and also can be used in the quality control of bulk manufacturing and pharmaceutical dosage forms.