Copper is an essential element that serves as cofactor for a number of oxygen-process enzymes involved in diverse biological processes. In excess, copper ions are highly toxic, thus proper copper trafficking is essential to cell vitality. Mutations in two copper transporting ATPases (ATP7A, ATP7B) lead to disorders of copper starvation (Menkes Disease) and toxicity (Wilson Disease), respectively, in humans. Recent studies show that the molecular components of copper trafficking pathways are highly conserved between yeast and human. In yeast, extracellular Cu2+ is reduced to Cu+ by metaloreductase enzymes encoded by fre1, fre2, fre7 and possibly other genes. Next, CTR1 and CTR3 transport Cu+ into the cell where cytoplasmic Cu+-chaperones deliver the metal to specific copper-dependent enzymes. LYS7 delivers Cu+ to Cu/Zn-superoxide dismutase, COX17 to cytochrome oxidase and ATX1 to CCC2. CCC2 is the yeast homologue of the Wilson and Menkes disease genes in humans. Ccc2 is located in the trans-Golgi network and transfers Cu+ to fet3 oxidase, which is a homologue of human ceruloplasmin. In yeast, two transcription factors are known to regulate copper metabolism, ACE1 and MAC1. Under conditions of copper starvation, MAC1 is stable and is bound to the copper-responsive promoter elements (CuREs) of fre1, fre2, fre7, ctr1 and ctr3. Under conditions of copper excess, MAC1 is rapidly degraded by autoproteolysis, thereby repressing expression of the copper uptake machinery. To further explore the mechanism of copper trafficking, we generated an S. cerevisiae strain lacking a functional MAC1 gene. We then compared genome-wide expression profiles of the mutant (mac1) and isogenic wild-type cells using yeast expression arrays. We will present the results of our expression analyses in light of copper trafficking pathways in yeast and humans.