Chemosensory information from peripheral arterial oxygen sensors in the carotid body (CB) is relayed by petrosal ganglion (PG) neurons to the center of respiration in the medulla oblongata. Biogenic amines, including histamine, released from sensor cells of the CB are considered to be primary transmitters in hypoxic chemosensitivity. Immunocytochemistry at light and electron microscopical levels and RT-PCR revealed the expression of histamine receptors 1 and 3 as well as histidine decarboxylase in the rat CB sensor cells and PG neurons. H1- and H3-receptors, but not histidine decarboxylase, were also observed in the ventrolateral, intermediate and commissural subnuclei of the nucleus tractus solitarii (NTS) in the medulla oblongata. In order to examine the possible role of histamine in the afferent branch of the respiratory system, we applied histamine receptors 1 and 3 agonists to the CB, which caused an increased phrenic nerve activity in a working heart-brainstem preparation. Moreover microinjection of antagonists of histamine receptors 1 and 3 into the NTS caused significant changes in the inspiratory timing and the chemoreceptor response. Our data show that histamine acting via H1- and H3-receptors plays an important role in the control of respiration.