Norepinephrine (NE) may be a neurotransmitter in a nociceptive pathway in the mesencephalic reticular formation (MRF) of the rat. When NE is applied microiontophoretically to certain neurons in rat MRF, it produces a change in neuronal firing rate similar to that produced by a noxious stimulus (foot pinch) in these neurons. If NE is a neurotransmitter involved in the transmission of nociceptive information in the MRF, specific adrenergic receptor antagonists, administered microiontophoretically, should block both the firing evoked by NE, administered microiontophoretically, and the firing evoked by foot pinch in these neurons. When phentolamine (an alpha adrenoceptor antagonist) was administered microiontophoretically it blocked the increases in neuronal firing rate evoked either by foot pinch or by NE. In contrast, propranolol (a beta adrenoceptor antagonist) rarely blocked the firing evoked by either foot pinch or by the microiontophoretic administration of NE. Thus, it appears that if NE is involved in the transmission of nociceptive information in the MRF of the rat, this information transfer is mediated by alpha adrenergic receptors.