Many species use chemical signals to convey information relevant to social and reproductive status between members of the same species (conspecific), but some chemical signals may also provide information to another species (heterospecific). Both of these types of complex chemical signals may be detected by the vomeronasal organ, which sends projections to the accessory olfactory bulb and on to the medial amygdala. Previous reports in hamster and mouse suggest that the medial amygdala sorts this complex chemosensory information categorically, according to its biological relevance (salience). In the present set of experiments, male mice having undergone vomeronasal removal surgery (VNX) or a sham-operation (SHAM) were exposed to conspecific (male and female mouse urine) or heterospecific (hamster vaginal fluid and worn cat collar) chemical stimuli. Similarly to our previous report with intact male mice [Samuelsen and Meredith (2009) Brain Res 1263:33-42], SHAM mice exhibit different immediate early gene (IEG) expression patterns in the medial amygdala dependent upon the biological relevance of the chemical stimuli. However, regardless of biological relevance, vomeronasal organ removal eliminates all responses in the medial amygdala to any of the chemical stimuli. Interestingly, VNX also disrupts the avoidance of (an unfamiliar) predator odor, worn cat collar. Here we show that the medial amygdala response to the tested chemical signals is dependent upon an intact vomeronasal organ.