A simple, sensitive and economical spectrophotometric method for simultaneously estimation of PRO and HCTZ. The first derivative (D1) of the UV spectrum was used in the determination of both drugs in their synthetic mixtures. The Peak to baseline and Peak area at suitable wavelengths were used in the study. The linearity of both drugs was up to a concentration of (5-40 µg/ml). The analytical results of the estimation of PRO were, Rec% 97.179-102.424% and RSD% 0.001-4.996 %. While for estimation of HCTZ were, Rec% between 95.406-103.681% and RSD% 0.001-3.676%. The method was accurate, good repeatability and successfully applied in the estimation of both drugs in their synthetic mixtures.