The olfactory system is thought to recognize odors with multiple odorant receptors (ORs) that are activated by overlapping sets of odorous molecules, ultimately generating an odor percept in the brain. We investigated how the odor percept differs between humans and Drosophila melanogaster fruit flies, species with very different OR repertoires. We devised high-throughput single fly behavior paradigms to ask how a given OR contributes to the odor percept in Drosophila. Wild-type flies showed dose-and stimulus-dependent responses to 70 of 73 odors tested, whereas mutant flies missing one OR showed subtle behavioral deficits that could not be predicted from the physiological responses of the OR. We measured human and fly judgments of odor intensity and quality and found that intensity perception is conserved between species, whereas quality judgments are species-specific. This study bridges the gap between the activation of olfactory sensory neurons and the odor percept.behavior ͉ Drosophila ͉ genetics ͉ olfaction ͉ psychophysics D espite the wealth of knowledge about the molecular basis of olfaction, little is known about how the odor percept forms in the brain. The identification of hundreds of odorant receptor (OR) genes (1), each encoding a different seven-transmembrane domain protein, provided an initial mechanistic explanation for how animals can discriminate a large number of chemical stimuli. Animals are thought to be able to identify and distinguish smells because each OR is activated by a specific set of odors and each odor activates a combination of ORs, a process known as combinatorial coding (2-6). A typical OR is sensitive to a few compounds at low concentrations and to a wider range of compounds at higher concentrations (5, 6). OR repertoires differ considerably in size between species, from Ϸ1,200 in rodents to Ϸ400 in humans, and 61 in the fly (Drosophila melanogaster) (7), but it is not well understood whether or how these differences impact odor perception across species. In this study, we investigate the influence of the OR repertoire on odor perception in humans and fruit flies. Both species exhibit robust responses to odors and cohabitate in most parts of the world (8) but have very different OR repertoires.Most of our knowledge about how an odor percept is experienced by the organism comes from experiments measuring odor perception in humans (9-12) because humans can selfreport their odor experience. Sensory parameters that can be measured in human odor perception by psychophysical techniques include odor intensity, distinguishability, similarity, and sensitivity to an odor. To link OR activation and the odor percept in flies, these parameters and concepts had to be transferred to Drosophila. This was problematic because little is known about how these insects respond behaviorally to odors.Here we report high-throughput behavioral assays that measure odor-evoked responses in single flies with great sensitivity and resolution. We used these assays to probe the sensitivity and receptive range o...