Two methods are described for the determination of theophylline (THP) and ephedrine hydrochloride (EPH) in combined pharmaceutical tablet forms. The first method depends on the use of the first derivative of the ratio-spectra obtained by dividing the absorption spectrum of binary mixtures by a standard spectrum of one of the compounds. The first derivative amplitudes at 231.8 and 250.3 nm were selected for the assay of THP and EPH, respectively. Calibration graphs were established for 20-180 mug ml(-1) for THP and 10-50 mug ml(-1) for EPH. The second method is based on high-performance liquid chromatography on a reversed-phase column using a mobile phase of methanol-water (40 + 60,v/v) (pH 3) with detection at 217 nm. Linearity was obtained in the concentration range of 5-150 mug ml(-1) for THP and 15-75 mug ml(-1) for EPH. The detection limits for THP and EPH were 0.73 and 0.92 mug ml(-1) by ratio-spectra derivative spectrophotometry and 0.59 and 0.86 mug ml(-1) by HPLC, respectively. The proposed methods were successfully applied to the determination of these drugs in laboratory-prepared mixtures and in tablets. The relative standard deviations were found to be less than 1.5%, indicating reasonable repeatibility of both methods. (C) 2002 Elsevier Science B.V. All rights reserved.