The vomeronasal organ (VNO) of mammals plays an essential role in the detection of pheromones. We obtained simultaneous recordings of action potentials from large subsets of VNO neurons. These cells responded to components of urine by increasing their firing rate. This chemosensory activation required phospholipase C function. Unlike most other sensory neurons, VNO neurons did not adapt under prolonged stimulus exposure. The full time course of the VNO spiking response is captured by a simple quantitative model of ligand binding. Many individual VNO neurons were strongly selective for either male or female mouse urine, with the effective concentrations differing as much as a thousandfold. These results establish a framework for understanding sensory coding in the vomeronasal system.