A simple, specific and accurate reverse phase high performance liquid chromatographic method was devel-oped for the simultaneous determination of dextromethorphan HBr (DM), phenylpropanolamine HCI (PE) and chlorpheniramine maleate (CPM), in syrup as pharmaceutical formulations. The final chromatographic conditions employed a Luna 5u C-18 (2) 100A [250 mm × 4.6 mm i.d] column. The mobile phase was 0.1% TEA in water + ACN (77 : 23%) v/y pH 3 to 3.05 with o-phosphorlc acid at a flow-rate of 1.5 ml/min. UV detection was performed at 260 nm for all the compounds. The retention times of dextromethorphan HBr (DM), chlorpheniramine maleate (CM) and phenyl propanolamine HCI (PE) were found to be 6.404, 3.595 and 1.673 min respectively. The method was validated in terms of linearity, range, specificity, accuracy, and precision, limit of detection (LOD) and limit of quantitation (LOQ). The linearity were found to be 1-400 ppm, and LOD were found to be 0.8, 0.16. 1 ppm the % recoveries were found to be 100.38%, 104.23%, 101.57%, respectively. The proposed method was successfully applied to the estimation of dextromethorphan HBr, and chlorpheniramine maleate, phenylpropanolamine HCI in combined tablet dosage forms. © 2015 Scientific Publishers. All Rights Reserved.