Sperm competition arises as a result of complex interactions among male and female factors. While the roles of some male factors are known, little is known of the molecules or mechanisms that underlie the female contribution to sperm competition. The genetic tools available for Drosophila allow us to identify, in an unbiased manner, candidate female genes that are critical for mediating sperm competition outcomes. We first screened for differences in female sperm storage and use patterns by characterizing the natural variation in sperm competition in a set of 39 lines from the sequenced Drosophila Genetic Reference Panel (DGRP) of wild-derived inbred lines. We found extensive female variation in sperm competition outcomes. To generate a list of candidate female genes for functional studies, we performed a genome-wide association mapping, utilizing the common single-nucleotide polymorphisms (SNPs) segregating in the DGRP lines. Surprisingly, SNPs within ion channel genes and other genes with roles in the nervous system were among the top associated SNPs. Knockdown studies of three candidate genes (para, Rab2, and Rim) in sensory neurons innervating the female reproductive tract indicate that some of these candidate female genes may affect sperm competition by modulating the neural input of these sensory neurons to the female reproductive tract. More extensive functional studies are needed to elucidate the exact role of all these candidate female genes in sperm competition. Nevertheless, the female nervous system appears to have a previously unappreciated role in sperm competition. Our results indicate that the study of female control of sperm competition should not be limited to female reproductive tract-specific genes, but should focus also on diverse biological pathways. I N many organisms, sperm competition is an important source of reproductive variation and is critical to the reproductive success of both males and females. Sperm competition occurs when a female mates with and stores sperm from multiple males. Multiple mating creates a situation in which the males' sperm "compete" for successful fertilizations. While the ultimate outcome of a sperm competition depends on a complex interaction between male and female factors, the sexes often have different interests. Males are essentially in competition with other males, and while natural selection drives males to become better competitors with each other, it may result in males damaging the female through toxicity of seminal proteins (Wigby and Chapman 2004;Mueller et al. 2007). On the other hand, females benefit from simply being able to produce the most and highest-fitness offspring, and this may entail a specific response to male-produced molecules that influence sperm competition. The sexual conflict that arises from these different evolutionary goals of males and females implies that the genetic response to selection on sperm competition may be totally distinct in males and females. It remains largely unknown what genes drive this sexual antagon...