It is commonly assumed that odorants are detected by the main olfactory epithelium (MOE) and pheromones are sensed through the vomeronasal organ (VNO). The complete loss of MOE-mediated olfaction in type-3 adenylyl cyclase knockout mice (AC3-/-) allowed us to examine chemosensory functions of the VNO in the absence of signaling through the MOE. Here we report that AC3-/- mice are able to detect certain volatile odorants via the VNO. These same odorants elicited electro-olfactogram transients in the VNO and MOE of wild-type mice, but only VNO responses in AC3-/- mice. This indicates that some odorants are detected through an AC3-independent pathway in the VNO.