Objective The aim of this study was to identify genes related to a heavy metal tolerance and to elucidate the tolerance mechanism in a eukaryote model using Saccharomyces cerevisiae. Results In this study, one strain tolerant to up to 50 mu M Pb(NO3)(2) and 30 mu M CdCl2 was isolated by screening a transposon-mediated mutant library and the disrupted gene was determined to be RIM15. In addition, this gene's characteristics related to heavy metals-tolerance was proved by deletion and overexpressing of this corresponding gene. The transposon mutant grew faster than the control strain and showed an obvious reduction in the intracellular level of reactive oxygen species (ROS) with activation of MSN4 and CTT1 in YPD medium containing 50 mu M Pb(NO3)(2) and 30 mu M CdCl2 respectively. Conclusions Disruption of RIM15 in S. cerevisiae results in increased tolerance to heavy metal stress.