CAX genes encode divalent cation/proton exchangers that are localized in the tonoplast (vacuole) membrane of plant cells. They transfer divalent-positive cations ( e.g. , Cd, Zn, Mn, Ca) from the cytosol to the vacuole sap where they may be sequestered. Our hypothesis was that addition of Arabidopsis CAX exchangers in root tonoplast would enhance vacuolar sequestration of Cd in roots under Cd exposure conditions found in the field, and thereby reduce Cd accumulation in leaves. We expressed AtCAX2 and AtCAX4, which are somewhat selective for Cd, Zn, Mn, in tobacco cv. KY14 using two different gene promoters that are highly active in roots. Experiments were made in 2004, 2005, and 2006 using different methods of leaf harvest. We observed a ~20 to 25% reduction in lamina Cd all three years, with no evidence for impact on yield. Results indicate that enhancing CAX transport in roots has potential to reduce Cd accumulation in lamina of tobacco and aerial tissues of crop plants.