In most mammals, the vomeronasal system has a pivotal role in mediating socio-sexual behaviours. The vomeronasal organ senses pheromones through the activation of specific receptors. Pheromone binding to cognate receptors activates Ca-influx via the gating of a cation channel that generates membrane depolarisation. The ex-vivo activation of vomeronasal neurons (VSNs) by pheromonal stimuli has been largely investigated by electrophysiological and imaging techniques; however, few studies have been carried out to determine the physiological responses of VSNs, in-vivo. By tracking the phosphorylation of S6 ribosomal protein as a marker of neuronal activity, we show that S6 becomes phosphorylated (pS6) in mouse VSNs stimulated by intraspecific and heterospecific pheromonal cues. We observed that female scent induces pS6 immunoreactivity in the apical VSNs of male vomeronasal epithelium, whereas male cues stimulate S6 phosphorylation in both the basal and apical VSNs of females. We also show that this dimorphic pattern of pS6 immunoreactivity is reproduced when heterospecific stimuli are used. Moreover, we found that a consistent proportion of VSNs is activated by both heterospecific and intraspecific pheromones. Additionally, we have evidence of adaptive responses to S6 phosphorylation when stimulation with cues of the same and opposite sex and of different species is sustained.