As the human genome project enters into the large-scale sequencing phase, one of the major challenges will be to assign functions to the tens of thousands of newly identified genes. Banfiet al. have developed a promising approach to this problem that utilizes both the power of Drosophila genetics and the extensive human andDrosophila genome database facilities now available. By searching a subset of the expressed sequence tag (EST) database for keywords corresponding toDrosophila genes, these authors identified 66 human genes, designatedDrosophila -related expressed sequences (DRES), that display significant homology to genes causing knownDrosophila mutant phenotypes. To determine whether any of the DRESs correspond to genes responsible for human disease, the DRES clones were assigned regional map positions using a combination of fluorescence in situ hybridization and radiation hybrid mapping. The availability of a human map position for a given DRES allowed the authors to compare information regarding human inherited disease loci mapping to the same or adjacent regions with the phenotype associated with mutations in the correspondingDrosophila gene. A large number of interesting potential relationships were found from such comparisons. For example, a DRES homologous to theDrosophila retinal degeneration B gene was mapped to human chromosome 11q13.5, a region to which several retinopathies have previously been mapped. While many such correlations will no doubt prove to be spurious, it will be surprising indeed if a number of them do not lead to the identification of previously unidentified human disease genes.