Cocaine abuse is a large social and economic problem that has received much public and scientific attention in recent years. Rodent and primate models have been used to study the behavioral and neurological effects of cocaine. Repeated intermittent doses of cocaine lead to progressive increases in both locomotor activity and stereotyped behaviors known as 'reverse tolerance' or behavioral sensitization, which may model the behavioral and neurochemical processes occurring in cocaine-addicted humans . The biological basis of sensitization is poorly understood. We report that free-base cocaine administered in volatile form to the fruit fly Drosophila melanogaster induces multiple reflexive motor responses that resemble cocaine-induced behaviors in rodents. These behaviors are both dose dependent and sexually dimorphic. Furthermore, Drosophila develops a behavioral sensitization to intermittent doses of cocaine. These results suggest that the pathways leading to cocaine-induced responses and sensitization are evolutionarily conserved between Drosophila and higher vertebrates, and that this genetically tractable animal can be used as a new model system to help determine the biological mechanisms underlying these processes.