Cadmium sulfide quantum dots (CdS QDs) are used in the manufacture of a number of electronics products. Their small size allows their ready entry into living cells, but as yet no attempt has been made to assess their toxicity. Our aim was to exploit two Ds transposition-induced mutant lines of Arabidopsis thaliana which tolerated exposure to CdS QDs to identify the genetic basis of their tolerance. Both a genome-wide top-down (from mutant to genes) and a bottom-up (from gene expression to phenotype) approach were applied. The differential responses of the mutants compared to the wild type showed that sensitivity to CdS QDs was unrelated to sensitivity to Cd(2+) ions. A transcriptomic analysis identified a number of genes whose transcript abundance was correlated with the tolerance. The phenotype of one of the mutants was correlated with the overexpression of ELM2, an MYB containing gene visited by a Ds transposon. Segregation analysis showed that the genetic basis of CdS QDs tolerance in both mutants was monogenic. The phenotype of the other mutant could be explained by the mutation of HCF101, a gene involved in photosynthesis.