The rodent vomeronasal system plays a critical role in mediating pheromone-evoked social and sexual behaviors. Recent studies of the anatomical and molecular architecture of the vomeronasal organ (VNO) and of its synaptic target, the accessory olfactory bulb (AOB), have suggested that unique features underlie vomeronasal sensory processing. However, the neuronal representation of pheromonal information leading to specific behavioral and endocrine responses has remained largely unexplored due to the experimental difficulty of precise stimulus delivery to the VNO. To determine the basic rules of information processing in the vomeronasal system, we developed a unique preparation that allows controlled and repeated stimulus delivery to the VNO and combined this approach with multisite recordings of neuronal activity in the AOB. We found that urine, a well-characterized pheromone source in mammals, as well as saliva, activates AOB neurons in a manner that reliably encodes the donor animal's sexual and genetic status. We also identified a significant fraction of AOB neurons that respond robustly and selectively to predator cues, suggesting an expanded role for the vomeronasal system in both conspecific and interspecific recognition. Further analysis reveals that mixed stimuli from distinct sources evoke synergistic responses in AOB neurons, thereby supporting the notion of integrative processing of chemosensory information.pheromones | sensory processing | vomeronasal | accessory olfactory bulb | mouse I n most animal species, the detection of pheromonal cues is essential to trigger and modulate sexual and social interactions between conspecifics. Genetic and surgical manipulations in the mouse have demonstrated the essential role of the vomeronasal system in this process (1-4). Moreover, tracing studies revealed dense projections from the vomeronasal system to hypothalamic nuclei involved in behavioral and endocrine control (5). The vomeronasal system thus offers a unique opportunity to explore principles of information processing underlying animal-animal communication and species-specific social and sexual interactions.Although the rodent vomeronasal system is clearly involved in pheromone sensing, the range of stimuli it can detect is largely unknown (5). At one extreme, it may be exclusively dedicated to processing pheromonal (i.e., conspecific) information. Consistent with this view, several classes of conspecific cues were shown to directly activate isolated vomeronasal organ (VNO) preparations (see ref. 6 for a recent review). Moreover, genetic as well as surgical VNO silencing significantly impairs behavioral responses to conspecific cues (1, 2). Alternatively, the vomeronasal system may resemble the main olfactory system in which a wide variety of stimuli, including both pheromonal and nonpheromonal signals, are processed. This idea is supported by the finding that in vitro VNO preparations can be activated by large sets of diverse chemicals (7,8).The type and specificity of information extracted by the acces...