Heavy metal is one of the major environmental pollutants. However the protective cellular mechanisms in response to heavy metal stress are not well-understood yet. Previously it has been found that the yeast deletion mutants lacking vacuolar H+-ATPase (V-ATPase) activity which functions in vacuolar acidification exhibited growth defects under cadmium stress conditions. In addition several genes involved in H+-ATPase have been recently found to be required for resistance to aluminum. To investigate the roles of vacuolar H+-ATPase plasma membrane H+-ATPase and mitochondrial H+-ATPase in tolerance to cadmium we examined the growth of yeast deletion mutants lacking different types of H+-ATPase in YPD media containing 80 μM of cadmium. Our results showed that a number of mutants lacking V-ATPase activity were sensitive to cadmium suggesting the important role of V-ATPase in cadmium detoxification. We next examined the growth of mutants lacking genes responsible for different vacuolar functions in order to investigate the functional activities of vacuoles involved in cadmium detoxification mechanism. We found that the mutants lacking vacuolar protein-sorting genes exhibited high sensitivity to cadmium as well suggesting the importance of protein transportation during cadmium stress.