AbstractSodium/calcium (Na+/Ca2+) exchangers are membrane transport systems that regulate Ca2+‐homeostasis in many eukaryotic cells. In olfactory and vomeronasal sensory neurons ligand‐induced olfactory signal transduction is associated with influx and elevation of intracellular Ca2+, [Ca2+]i. While much effort has been devoted to the characterization of Ca2+‐related excitation and adaptation events of olfactory chemosensory neurons (OSNs), much less is known about mechanisms that return [Ca2+]i to the resting state. To identify proteins participating in the poststimulus Ca2+‐clearance of mouse OSNs, we analyzed the expression of three potassium (K+)‐independent (NCX1, 2, 3) and three K+‐dependent (NCKX1, 2, 3) Na+/Ca2+ exchangers. In situ hybridization showed that mRNAs of all six Na+/Ca2+ exchangers coexist in neurons of the olfactory and vomeronasal systems, and that some are already detectable in the embryo. Of these, NCX1 and NCKX1 represent the most and least abundant mRNAs, respectively. Moreover, immunohistochemistry revealed that the NCX1, 2, and 3 proteins are expressed in nearly all neurons of the olfactory epithelium, the vomeronasal organ, the septal organ of Masera, and the Grueneberg ganglion. These three exchanger proteins display different expression profiles in dendrites, knobs, and plasma membranes of OSNs and in sustentacular cells. Furthermore, we show that NCX1 mRNA in rat olfactory mucosa is expressed as 8 alternative splice variants. This is the first comprehensive analysis of Na+/Ca2+ exchanger expression in the mammalian olfactory system. Our results suggest that Ca2+‐extrusion by OSNs utilizes multiple different Na+/Ca2+ exchangers and that different subtypes are targeted to different subcellular compartments. J. Comp. Neurol. 501:944–958, 2007. © 2007 Wiley‐Liss, Inc.