Detection and transduction of pheromonal signals by the mouse vomeronasal organ (VNO) is critical for the formation of a persistent memory required for mate recognition in the context of selective pregnancy failure (the Bruce effect). This pregnancy block can be mediated by peptide ligands of disparate major histocompatibility complex (MHC) molecules, but little is known about the molecular mechanisms underlying this effect. Given the proposed key role of the transient receptor potential channel, TRPC2, in VNO signal transduction, we tested whether TRPC2 is essential for memory formation in the context of the Bruce effect. Surprisingly, the loss of the TRPC2 channel did not significantly influence memory formation, whereas surgical lesions of the VNO caused a profound deficit. Furthermore, field potential and single-cell patch-clamp recordings showed that TRPC2 is dispensable for the transduction of MHC peptide ligands by sensory neurons in the basal zone of the VNO. This indicates that a previously unrecognized TRPC2-independent signal transduction mechanism in the VNO underlies the sensing of cues required for the formation of this pheromonal recognition memory.