ABSTRACT The yeast vacuolar proton-translocating ATPase was discovered in 1981 as the first member of the V-ATPases, which are now known to be ubiquitously distributed in eukaryotic vacuo-lysosomal organelles and archaebacteria. Nine VMA genes that are indispensable for expression of vacuolar ATPase activity have been identified in the yeast Saccharomyces cerevisiae. VMA1, VMA2, VMA3, VMA5 and VMA6 were cloned and characterized on the basis of partial amino acid sequences determined with the purified subunits. Genetic and biochemical studies of the yeast Pet–cls mutants have demonstrated that they are related to vma defects. Based on this evidence, VMA11 (CLS9), VMA 12 (CLS10) and VMA 13 (CLS11) were isolated from a yeast genomic DNA library by complementation of the vmal 1, vma!2 and vma!3 mutations, respectively. This article summarizes currently available information on the VMA genes and the molecular biological functions of the VMA gene products.