Derivative UV spectrophotometry is well established for analysing pharmaceutical products containing more than one drug. By contrast, the least-squares method for over-determined systems is rarely used, because it is assumed that measurements at a large number of wavelengths are needed to obtain good results. Both methods have advantages, and their use in combination is useful for analysing polypharmaceuticals. A combination of derivative and least-squares methods was used to analyse tablets containing pseudoephedrine hydrochloride, triprolidine hydrochloride and dextromethorphan hydrobromide. Pseudoephedrine was determined by derivative spectrophotometry. The other drugs were determined by the least-squares method at higher wavelengths where pseudoephedrine does not absorb. Satisfactory precision for the least-squares method was obtained with a manual spectrometer measuring at six wavelengths and calculating the results with a microcomputer.