We studied the functional characteristics of the vomeronasal system in clinically normal adult subjects of both sexes (ages 20-45). Chemosensory substances were administered in punctate pulses in a continuous air stream from the tip of a multifunctional miniprobe, which contained a nonpolarizable electrode. Negative potentials with the characteristics of receptor potentials were recorded from the surface of the vomeronasal organ (VNO) and olfactory epithelium (OE) in response to certain substances defined here as vomeropherins (see definition in the introduction of the main text) and to olfactants. Stimulation of the VNO with femtomole amounts of vomeropherins produced a local depolarization with the characteristics of a receptor potential. The same substances produced only a small response from the OE, and no response from the nasal respiratory mucosa. Three vomeropherins PH15, PH78, and PH84 were particularly well recognized by the VNO of most male subjects (p < .01; n = 30). Substances PH30, PH56, and PH94B, produced similar effects in the VNO of most female subjects (p < .01; n = 30). Responses to virtually all vomeropherins exhibited a sexual dimorphism. Stimulation of the OE with the same quantity of odorants 1,8-cineole and l-carvone produced depolarization of 6.8 +/- 2.6 mV, but little or no response in the VNO. Therefore, the human VNO seems to have a unique specificity for certain chemosensory substances when compared to the OE. Administration of PH15 and PH78 to the VNO of male subjects (but not to female subjects) significantly increased electrodermal activity (p < .02) and skin temperature (p < .01). On the other hand, administration of PH84 to the VNO of male subjects decreased skin temperature but had little effect on electrodermal activity. Autonomic changes were accompanied by an increased percentage of alpha-cortical activity for all three vomeropherins. In female subjects (but not in male subjects) vomeropherins PH56 and PH94B significantly increased electrodermal activity (p < .01), skin temperature (p < .01), and alpha-cortical activity (p < .01). Local application of the olfactants 1,8-cineole and l-carvone to the VNO did not trigger autonomic responses or significant changes in the electroencephalographic pattern in male or in female subjects. Our studies indicate the adult human VNO is a functional chemosensory organ with a sexually dimorphic specificity and the ability to transduce signals which modulate certain autonomic parameters.