The yeast YRR1 gene was identified as a sequence encoding a protein that is related in structure to the Pdr1 and Pdr3 zinc cluster transcription factors. Dominant gain-of-function mutations were recovered that cause a multidrug resistance to inhibitors transported by the SNQ2 and YOR1 proteins. It was previously reported by others that null mutations in YRR1 cause hypersensitivity to these agents. In this study, evidence is presented for allelism between YRR1 and a previously identified locus: PDR2. Further characterization of hyperresistant PDR2 alleles and the initial characterization of a loss-of-function mutation created by a Tn3 insertion are described. Surprisingly, the PDR2-2-mediated hyperresistance to chloramphenicol, anisomycin, and cycloheximide requires the function of the UBP6 gene and at least one other gene product. The PDR2-2 allele eliminates the requirement for Pdr1 although, in our genetic backgrounds, elimination of Pdr2 function has little or no phenotypic effect.