The Drosophila gene fruitless expresses male and female specific transcription factors which are responsible for the generation of male specific neuronal circuitry for courtship behavior. Mutations in this gene may lead to bisexual behavior in males. Bisexual behavior in males also occurs in the absence of the neuropeptide SIFamide. We show here that the SIFamide neurons do not express fruitless. However, when fruitless neurons are made to express RNAi specific for the SIFamide receptor, male flies engage in bisexual behavior, showing that SIFamide acts on fruitless neurons. If neurons expressing a SIFaR-gal4 transgene are killed by the apoptotic protein reaper or when these neurons express SIFamide receptor RNAi, males also show male–male courtship behavior. We next used this transgene to localize neurons that express the SIFamide receptor. Such neurons are ubiquitously present in the central nervous and we also found two neurons in the uterus that project into the central nervous system.