Two spectrophotometric methods were applied to the simultaneous assay of chlorhexidine hydrochloride (CHL) and lidocaine hydrochloride (LIH) in pharmaceutical formulations. Using derivative spectrophotometry, CHL was determined by measurement of its first derivative signal at 290 nm (peak to zero amplitude) in the concentration range 5-9 mu g/mL, and LIH was analysed by measurement of its second derivative signals at 272 and 276 nm (peak to peak amplitude) in the concentration range 160-480 mu g/mL. With the partial least-squares (PLS-2), the experimental calibration matrix was constructed using 9 samples. The concentration ranges considered were 5-7 mu g/mL for CHL and 220, 240, 260 mu g/mL for LIH. The absorbances were recorded between 240 and 310 nm at every 5 nm.