Electrical stimulation in the nucleus reticularis gigantocellularis (NGC) and gigantocellularis pars alpha (NGC alpha) produces facilitation and/or inhibition of spinal nociceptive transmission in behavioral and electrophysiological studies. The present study examined spinal neurotransmitter receptors mediating descending facilitation from the NGC/NGC alpha. As previously demonstrated, electrical stimulation in the NGC/NGC alpha at low intensities (approximately equal to 10 microA) produced facilitation and at greater intensities (approximately equal to 38 microA) inhibition of the tail-flick (TF) reflex. Intrathecal pretreatment with the non-selective serotonin (5-HT) receptor antagonist methysergide attenuated or completely abolished facilitation of the TF reflex produced by electrical stimulation in the NGC/NGC alpha; intrathecal pretreatment with atropine, phentolamine, naloxone or mecamylamine was without effect on stimulation-produced facilitation. Descending inhibition from the NGC/NGC alpha produced by electrical stimulation was attenuated or completely abolished by bilateral transection of the dorsolateral funiculi (DLF) of the cervical spinal cord. Descending facilitation produced by electrical stimulation, however, was unaffected or enhanced following DLF transections. Glutamate microinjections (1.7 nmol/0.17 microliters) into the NGC/NGC alpha produced a rapid, repeatable and short-duration facilitation of the TF reflex in rats with bilateral DLF transections and such facilitation was attenuated by intrathecal pretreatment with methysergide, but not atropine, xylamidine (5-HT2 selective receptor antagonist) or MDL-72222 (5-HT3 selective receptor antagonist). These findings suggest that facilitation of the TF reflex from the activation of the cell bodies in the NGC/NGC alpha is mediated by a descending serotonergic pathway traveling in the ventrolateral funiculi and by spinal 5-HT1 receptors.