An integrated molecular and physiological investigation of the fundamental mechanisms of heavy metal accumulation was conducted in Thlaspi caerulescens, a Zn͞Cd-hyperaccumulating plant species. A heavy metal transporter cDNA, ZNT1, was cloned from T. caerulescens through functional complementation in yeast and was shown to mediate high-affinity Zn 2؉ uptake as well as lowaffinity Cd 2؉ uptake. It was found that this transporter is expressed at very high levels in roots and shoots of the hyperaccumulator. A study of ZNT1 expression and high-affinity Zn 2؉ uptake in roots of T. caerulescens and in a related nonaccumulator, Thlaspi arvense, showed that alteration in the regulation of ZNT1 gene expression by plant Zn status results in the overexpression of this transporter and in increased Zn influx in roots of the hyperaccumulating Thlaspi species. These findings yield insights into the molecular regulation and control of plant heavy metal and micronutrient accumulation and homeostasis, as well as provide information that will contribute to the advancement of phytoremediation by the future engineering of plants with improved heavy metal uptake and tolerance. R ecently, there has been considerable interest in the use of terrestrial plants as a green technology for the remediation of surface soils contaminated with toxic heavy metals. This technology, termed phytoremediation, uses plants to extract heavy metals from the soil and to concentrate them in the harvestable shoot tissue (1, 2). A major factor behind the interest in phytoremediation of metal-polluted soils has been the growing awareness of the existence of a number of metalaccumulating plant species. These plant species, called hyperaccumulators, are endemic to metalliferous soils and can accumulate and tolerate high levels of heavy metals in the shoot (3, 4). Among the best known hyperaccumulators is Thlaspi caerulescens. This member of the Brassicaceae family has attracted the interest of plant biologists for over a century because of its ability to colonize calamine and serpentine soils containing naturally elevated levels of heavy metals such as Zn, Pb, Cd, Ni, Cr, and Co.