The mosquito Anopheles gambiae is the principal Afrotropical vector for human malaria. A central component of its vectorial capacity is the ability to maintain sufficient populations of adults. During both adult and preadult (larval) stages, the mosquitoes depend on the ability to recognize and respond to chemical cues that mediate feeding and survival. In this study, we used a behavioral assay to identify a range of odorant-specific responses of An. gambiae larvae that are dependent on the integrity of the larval antennae. Parallel molecular analyses have identified a subset of the An. gambiae odorant receptors (AgOrs) that are localized to discrete neurons within the larval antennae and facilitate odor-evoked responses in Xenopus oocytes that are consistent with the larval behavioral spectrum. These studies shed light on chemosensory-driven behaviors and represent molecular and cellular characterization of olfactory processes in mosquito larvae. These advances may ultimately enhance the development of vector control strategies, targeting olfactory pathways in larval-stage mosquitoes to reduce the catastrophic effects of malaria and other diseases.malaria ͉ olfaction ͉ signal transduction ͉ odorant receptors S ensitivity and the ability to respond to a wide range of olfactory cues are essential for many behavioral processes that mediate the vectorial capacity of Anopheles gambiae and other diseasecarrying mosquitoes (1). Although there is a growing body of knowledge of the adult An. gambiae olfactory system, there is a paucity of information as to the molecular and cellular basis of olfaction in larval stages, in which it may be of potential importance in disease control. Paradoxically, despite being one of the historically most successful strategies for mosquito control (2) and prevention of human malaria, the targeting of mosquito larvae or larval habitats around human dwellings is sparsely implemented in Africa and other malaria-endemic regions (3). Furthermore, the simplicity of insect larval olfactory systems makes them excellent models to study olfactory signal transduction and coding. Indeed, the arbovirus vector mosquito Aedes aegypti expresses 24 odorant receptor (OR) genes in the larval antenna, 15 of which are larval specific (4). Elegant work in the Drosophila melanogaster model has detailed larval behavioral responses and characterized 25 ORs that are expressed in 21 olfactory receptor neurons (ORNs) in each of the two dorsal organs, which constitute the olfactory apparatus of the fly larva (5-7).In this study, we designed and used a simple olfactory-based assay to carry out an initial characterization of An. gambiae larval behavioral responses to a range of natural and synthetic chemical stimuli. Consistent with olfactory function, ablation of the larval antennae specifically eliminated these behavioral responses, and molecular approaches identified a set of larval AgOrs, which were in some cases larval specific and the transcripts of which were mapped to a distinctive population of ORNs within th...