Targeted manipulation of the genome is used to analyze gene expression, genome structure and protein structure. In yeast it has long been possible to introduce sequences into predetermined sites in the genome by double-strand break (DSB) repair (1 ). Until recently, such specificity has eluded investigators that useDrosophilaas their model organism. Such a gene-targeting system is now available inDrosophila. The system is based on the repair of a specific DSB made by P element excision (2 –12 ).