Animal olfactory systems detect environmental volatile chemicals and integrate this information to direct discovery of food and mates and avoidance of danger. Rather than remaining constant, olfactory response thresholds are modulated by internal and external cues to adapt odor-guided behaviors to changing conditions. Here, we show in Drosophila melanogaster that neuropeptide F (NPF) modulates the responses of a specific population of the antennal olfactory sensory neurons (OSNs) to food-derived odors. We show knock-down of NPF in NPF neurons specifically reduces the responses of the ab3A neurons to ethyl butyrate, a volatile ester found in apples and other fruits. Knock-down of the NPF receptor (NPFR) in the ab3A neuron reduces their responses and disrupts the ability of the flies to locate food. We also identify a sexual dimorphism in ab3A responsiveness: ab3A neurons in females immediately post-eclosion are less responsive to ethyl butyrate than those of both age-matched males and older females. Not only does this change correlate with brain NPF levels, NPFR mutants show no such sexual dimorphism. Finally, by way of mechanism, we show mutation of NPFR seems to cause intracellular clustering of OR22a, the odorant receptor (OR) expressed in the ab3A neurons.