Zinc can occur in extremely high concentrations in acidic, heavy metal polluted environments habited by acidophilic prokaryotes. Although these organisms are able to thrive in such severely ntaminated ecosystems their resistance mechanisms have not been well studied. Bioinformatic alysis of a range of acidophilic bacterial and archaeal genomes identified homologues of several own zinc homeostasis systems. These included primary and secondary transporters, such as the imary heavy metal exporter ZntA and Nramp super-family secondary importer MntH. Three idophilic model microorganisms, the archaeon 'Ferroplasma acidarmanus', the Gram negative cterium Acidithiobacillus caldus, and the Gram positive bacterium Acidimicrobium ferrooxidans, were lected for detailed analyses. Zinc speciation modeling of the growth media demonstrated that a large action of the free metal ion is complexed, potentially affecting its toxicity. Indeed, many of the tative zinc homeos! asis genes were constitutively expressed and with the exception of 'F. acidarmanus' ZntA, they were t up-regulated in the presence of excess zinc. Proteomic analysis revealed that zinc played a role in idative stress in At. caldus and Am. ferrooxidans. Furthermore, 'F. acidarmanus' kept a constant level intracellular zinc over all conditions tested whereas the intracellular levels increased with increasing nc exposure in the remaining organisms.