The mechanisms by which vanadate exerts a toxic effect on living organisms are not completely understood. This is principally due to the variety of intracellular targets of the metal and to the changes in the chemical form and oxidation states that vanadate can undergo, both in the external environment and intracellularly. In order to further elucidate the reasons for vanadate toxicity, and assuming that common detoxification mechanisms can be evoked by a general heavy metal response, we have compared some aspects of the cellular responses to vanadate and copper in the yeast Hansenula polymorpha. By means of 2D electrophoresis we show the existence of common determinants in the responses to vanadate- and copper-induced stresses. Moreover, we demonstrate that both metals induce significant increases in antioxidant enzyme levels, and that there are significant overlaps in the heavy metal and oxidative stress responses. Interestingly, vanadate induces an increase in catalase activity that is much higher than that seen with copper and, unlike copper, does not cause lipid peroxidation of cellular membranes. This suggests that H. polymorpha cells activate a further specific detoxification pathway against vanadate-induced oxidative insults.