Three spectrophotometric methods for simultaneous determination of pseudoephedrine sulfate and dexbrompheniramine maleate based on total absorbance measurements and processing of the results by partial least-squares regression (PLS-1), principal component regression (PCR), and artificial neural networks (ANN) have been proposed. For calibration, the concentration data matrix was prepared using synthetic solutions of pseudoephedrine sulfate and dexbrompheniramine maleate in 0.1 mol L-1 HCl. The absorbance data matrix corresponding to the concentration data matrix was obtained by measuring absorbance values at 19 wavelengths in the range 242-278 nm, each Δλ = 2 nm in the zero-order spectra in PCR, PLS-1, and ANN. The procedures did not require any separation step. The lower limit of quantitation was 200 mg mL-1 for pseudoephedrine sulfate and 10 mg mL-1 for dexbrompheniramine maleate. All methods were validated by analysing laboratory-made samples. The proposed three methods were successfully applied to the analysis of a pharmaceutical formulation - a sugar-coated tablet; the results were compared mutually and with the data obtained by the LC method. The total duration of the chromatographic analysis was 6 min.