The effects of elevated CO2(i.e. hypercapnia) on neurons in the nucleus tractus solitarii were studied using extracellular (n = 82) and intracellular (n = 33) recording techniques in transverse brain slices prepared from rat. Synaptic connections from putative chemosensitive neurons in the ventrolateral medulla were removed by bisecting each transverse slice and discarding the ventral half. In addition, the response to hypercapnia in 20 neurons was studied during high magnesium low calcium synaptic blockade. Sixty-five per cent of the neurons (n = 75) tested were either insensitive or inhibited by hypercapnia. However, 35% (n = 40) were depolarized and/or increased their firing rate during hypercapnia. Nine out of 10 CO2 excited neurons retained their chemosensitivity to CO2 in the presence of high magnesium low calcium synaptic blockade medium. Our findings demonstrate that many neurons in the nucleus tractus solitarii were depolarized and/or increased their firing rate during hypercapnia. These neurons were not driven synaptically by putative chemosensitive neurons of the ventrolateral medulla since this region was removed from the slice. Furthermore, because chemosensitivity persisted in most neurons tested during synaptic blockade, we conclude that some neurons in the nucleus tractus solitarii are inherently CO2-chemosensitive. Although the function of dorsal medullary chemosensitive neurons cannot be determined in vitro, their location and their inherent chemosensitivity suggest a role in cardiorespiratory central chemoreception. © 1990.