A novel Saccharomyces cerevisiae (Sc) SVS1 gene was cloned as a multicopy suppressor of vanadate (Vn) sensitivity (VnS) due to a calcineurin (CaN) null mutation. SVS1 encoded a 260-amino-acid protein abundant in Ser and Thr residues, with a putative signal sequence at the N terminus. Deletion of SVS1 resulted in increased sensitivity to Vn, but not to other metallic ions or drugs. Northern analysis of the SVS1 mRNA indicated that the induction of the gene occurred specifically in the response to Vn. These results suggested that Sc has a mechanism to enhance the tolerance to Vn by increasing the expression of SVS1. The results of genetic experiments suggested that CaN and the Svs1 proteins act in separate pathways to enhance the tolerance to Vn.