The use of microemulsions as eluents in HPLC has shown excellent potential. We have developed a novel, rapid and sensitive microemulsion HPLC (MELC) method using oil-in-water microemulsion mobilephase for the simultaneous determination of a binary mixture of cetirizine hydrochloride (CTZ) and ambroxol hydrochloride (AMB) in pure form and in their tablet formulation. The analysis was achieved using 150 mm x 4.6 mm cyano-column. Mobile phase, containing 0.20M sodium dodecyl-sulfate, 15% propanol and 0.15 triethylamine, adjusted to pH 3.0 with orthophosphoric acid, was pumped at a flow rate of 1.0 mL min-1 with UV-detection at 230 nm. The method showed good linearity in the range of 1.0-10.0 μg mL-1 and 5-100 μg mL-1, detection limit of 0.037 and 0.228 μg mL-1 and quantitation limit of 0.039 and 0.691 μg mL-1 for CTZ and ABM, respectively. The influence of the composition of the microemulsion system was studied and the method was found to be robust with respect to some changes of the microemulsion components.