A recent article in Science (288, 2013–2017, 2000) describes the first gene targeting technology for the fruit fly, Drosophila melanogaster. Until now, attempts at gene targeting in Drosophila have been limited to transposable P elements, which insert genes randomly into the genome. Authors Kent Golic and Yikang Rong accomplished specific targeting by first randomly introducing a heat-inducible site-specific I-SceI endonuclease and FLP recombinase using the P element system. They subsequently transformed the FLP/I-SceI flies with a targeting construct that contained a cloned copy of the gene of interest (Drosophila yellow+) flanked by FLP recombination target sites. They showed that 55 of 56 transformants detected had integrated yellow+ at the target locus. Although critics suggest that the events may have been due to breakage-induced replication close to the telomere, Golic is further characterizing the system to validate the specificity of gene targeting and to increase targeting efficiency. With at least 177 genes shared between humans and fruit flies, the system should prove useful in functional genomics.