The closest that Drosophila geneticists have come to 'reverse genetics' thus far has been the fortuitous insertion of a transposable P element in or near their gene of interest. In the 16 June Science, Rong and Golic present a system that may allow the mutagenesis of a specific gene by homologous recombination (Science 2000, 288:2013-2018). They introduce three elements into flies: the FRT recombinase, a rare-cutting endonuclease, and a copy of the target DNA with sites for the FRT recombinase at either end. When induced, the recombinase converts the introduced DNA into a circle, which is then linearized by the endonuclease. This double-stranded break is recombinogenic. Although Rong and Golic restore function to a previously mutated gene, use of a vector modified to look like yeast knockout vectors should produce knockouts in flies.