A conformational conversion of the cellular prion protein (PrPC) is now recognized as the causal event of fatal neurodegenerative disorders, known as prion diseases. In spite of long-lasting efforts, however, the physiological role of PrPC remains unclear. It has been reported that PrPC is expressed in various areas of the olfactory system, including the olfactory epithelium, but its precise localization in olfactory sensory neurons (OSNs) is still debated. Here, using immunohistochemistry tools, we have reinvestigated the expression and localization of PrPC in the olfactory epithelium of adult congenic mice expressing different PrPC amounts, that is, wild-type, PrP-knockout, and transgenic PrPC-overexpressing animals. We found that PrPC was expressed in OSNs, in which, however, it was unevenly distributed, being detectable at low levels in cell bodies, dendrites and apical layer, and more abundantly in axons. We also studied the involvement of PrPC in the response of the olfactory epithelium to odorants, by comparing the electro-olfactograms of the 3 mouse lines subjected to different stimulation protocols. We found no significant difference between the 3 PrP genotypes, supporting previous reports that exclude a direct action of PrPC in the early signal transduction activity of the olfactory epithelium.