The polarographic behaviour of the sulfonamides sulfadiazine, sulfamerazine and sulfamethazine was studied in Britton–Robinson buffer solutions. These compounds show well defined reduction waves and differentiated peaks in differential-pulse polarography (DPP) with E_p values near –700, –790 and –1140 mV, respectively, in an acidic medium (approximately pH 2), the behaviour of the sulfonamides in response to variations in pH and concentration is very similar. However, when two or three of these compounds are present together, the signal obtained in DPP does not agree with the superposition of the signal of each one of them when present alone. This fact can be explained by the change that the dc wave corresponding to any of the sulfonamides undergoes owing to the presence of one or two of the others, thus making the direct analysis of their mixtures by DPP impossible. The ability of partial least squares multivariate methods to resolve this problem was examined. In general, good results were obtained and the method was applied to the analysis of mixtures of these sulfonamides in veterinary and pharmaceutical formulations.