These electrophysiological investigations of spinal cord neurones responding to noxious and non-noxious cutaneous stimulation were conducted to evaluate (1) their ascending projection into the spinothalamic tract, (2) the involvement of endogenous opioids in mediating the tonic descending and segmental inhibition and (3) the role of the nucleus locus coeruleus (LC) in modulating spinal cord nociceptive transmission A total of 252 neurones were antidromically activated from the ventrolateral quadrant but only 14 of these were found to project into the spinothalamic tract. The spinothalamic tract (STT) neurones responded to noxious and non-noxious, or to noxious stimulation alone. All the units were located in lamina VII and most of them displayed wide receptive fields. None of the 39 specific nociceptor-driven neurones from lamina I was found to project into the spinothalamic tract. Naloxone (0.3-2.0 mgm/kg) did not alter the response of multireceptive neurones to heat, to tonic descending inhibition or to the inhibition generated by stimulation of contralateral plantar nerve or dorsal columns. Stimulation in the nucleus locus coeruleus produced a predominantly inhibitory effect on nociceptive transmission in the spinal cord. The descending inhibition produced from LC was antagonised by the administration of a-noradrenergic receptor antagonists but was not changed by 3-receptor antagonists. Methysergide did not alter the inhibition from LC or NRM whereas the GABA antagonist, bicuculline, abolished the inhibition. Naloxone partially reduced the inhibition from LC. The ipsilateral ventral quadrant lesion (VLF and VF) abolished the actions produced from LC but a bilateral DLF lesion was required for abolishing the NRM actions. Electrolytic lesions made in the midline raphe complex did not block the actions produced from LC. The stimuli in LC and NKM that evoked inhibition of multireceptive neurones also produced DRPs. These data support the conclusion that the spinothalamic tract in the cat plays a role in the transmission of nociceptive and tactile messages to the brain. The endogenous opioids do not appear to be involved in mediating the types of inhibition examined (Section III). The descending actions produced from LC are not mediated through NRM and are most probably mediated through the direct coeruleospinal projection. Catecholaminergic, opioid and Gabaergic transmission is involved in mediating these actions which may involve both the pre- and postsynaptic mechanisms.