The formyl peptide receptor (Fpr) family is well known for its contribution to immune defense against pathogens in human and rodent leucocytes. Recently, several structurally related family members were discovered in sensory neurons of the mouse nose, i.e. the vomeronasal organ (VNO). Although the biological role of vomeronasal Fprs is not yet clear, the contribution of other Fprs to host immune defense suggested that they contribute to vomeronasal pathogen sensing. Precise knowledge about the agonist properties of mouse Fprs is required to ultimately determine their function. We expressed all seven mouse and three human Fprs using an in vitro system and tested their activation by conducting high throughput calcium measurements. We found an intriguing functional conservation between human and mouse immune Fprs that is most likely a consequence of closely similar biological constraints. By contrast, our data suggest a neofunctionalization of vomeronasal Fprs. The vomeronasal receptor mFpr-rs1 is activated by W-peptide and structural derivatives but not by other typical ligands of immune Fprs. We identified a key agonist motif for the receptor frequently occurring in bacteria. Thus, the ligand profile of mFpr-rs1 is consistent with a role in vomeronasal pathogen sensing. To investigate the physiological response of the VNO towards W-peptide, we established a novel high-throughput calcium imaging assay that permits the functional analysis of large numbers of individual, dissociated vomeronasal sensory neurons. Intriguingly, we observed a small subset of sensory VNO-neurons that showed a stereo selective agonist profile which is similar to that of heterologously expressed mFpr-rs1.