It is reported that some of the widely used laboratory strains of Saccharomyces cerevisiae (e.g. W303, BY4741) are sensitive to synthetic media containing all 20 amino acids [e.g. synthetic complete (SC) medium or supplemented minimal medium]. To determine the molecular basis for this unexpected sensitivity, a genomic library was screened and three genes were identified that, when overexpressed, rescue cells from this phenotype. Two of the 'rescuing' genes, BAP2 and TAT1, are related to transport of leucine, and one, LEU2, to synthesis of leucine, showing that sensitivity to SC medium is associated with the leu2 mutation. The sensitive strains seem incapable of transporting leucine when grown on synthetic complete media. This effect of the leu2 mutation should be taken into consideration when analyzing the results of genetic screens and other experiments performed with these strains.