We know little about several important properties of beneficial mutations, including their mutational origin, their phenotypic effects (e.g., protein structure changes vs. regulatory changes), and the frequency and rapidity with which they become fixed in a population. One signature of the spread of beneficial mutations is the reduction of heterozygosity at linked sites. Here, we present population genetic data from several loci across chromosome arm 2R in Drosophila simulans. A 100-kb segment from a freely recombining region of this chromosome shows extremely reduced heterozygosity in a California population sample, yet typical levels of divergence between species, suggesting that at least one episode of strong directional selection has occurred in the region. The 5' flanking sequence of one gene in this region, Cyp6g1 (a cytochrome P450), is nearly fixed for a Doc transposable element insertion. Presence of the insertion is correlated with increased transcript abundance of Cyp6g1, a phenotype previously shown to be associated with insecticide resistance in Drosophila melanogaster. Surveys of nucleotide variation in the same genomic region in an African D. simulans population revealed no evidence for a high-frequency Doc element and no evidence for reduced polymorphism. These data are consistent with the notion that the Doc element is a geographically restricted beneficial mutation. Data from D. simulans Cyp6g1 are paralleled in many respects by data from its sister species D. melanogaster.