Using two statistical models, based on the two-level full factorial designs and sequential experimental Doehlert designs, a simultaneous determination of cadmium and zinc by solid-phase derivative spectrophotometry has been proposed. These chemometric techniques have been used for the optimization of the instrumental and experimental variables of the system. The complexes formed between cadmium and zinc with 4-(2-pyridylazo) resorcinol, in the presence of potassium iodide, were fixed on a dextran-type anion-exchange gel, at pH 8.7. The absorbance spectra of the gel, packed in a 1-mm cell, were recorded directly. The performance characteristics of the proposed method have been established. The method was applied to the simultaneous determination of both analytes in synthetic mixtures and natural water samples.