Sulfa drugs have been used as antimicrobials for decades but resistance is now a problem. For major eukaryotic pathogens, including Plasmodium and Pneumocystis, sulfa drug testing is difficult or impossible. We have shown that the eukaryote yeast can be used as a model for the study of sulfa drugs within certain parameters. Fifteen sulfa drugs inhibited yeast growth in a manner indicating competition with p-aminobenzoate (pABA). Such competition resulted from direct addition of pABA or through increased expression of the pABA synthase gene (ABZ1). The model system predicts that overexpression of the pABA synthase gene can lead to drug resistance.