Exploratory outlier identification methods and confirmatory gene expression studies showed induction of the iron regulon in Saccharomyces cerevisiae lacking Mac1p, a copper-responsive transcription factor. The Aft1p/Aft2p binding motif was the most discriminating motif between up- and down-regulated genes, and we identified new genes potentially regulated by Aft1p/Aft2p. In addition, multiple genes encoding proteins containing Fe-S clusters were down-regulated suggesting metabolic reorganization to conserve iron in mac1Delta. Null mutants of each of the differentially expressed genes were characterized for copper- or iron-related phenotypes. New or additional support for a role in copper and iron homeostasis is provided in this study for the gene products of AKR1, MRS4, PCA1, SSU1, TIS11, YBR047W, YHL035C, YHR045W, YLR047C, YLR126C, and YTP1.