In lightly pentobarbital-anesthetized and acutely prepared rats, electrical stimulation within the arcuate nucleus of the hypothalamus (ARH) consistently inhibited the tail-flick responses to noxious heating of the tail. The peptide ICI174864, a delta-opioid receptor antagonist applied intrathecally at the lumbar level at a dose of 1 nmol, markedly attenuated this inhibition without affecting the baseline nociceptive threshold. Normal saline injected by the same approach had no effect on the ARH inhibitory modulation. This is the first report showing an involvement of the delta-opioid receptor in the descending inhibition of spinal nociceptive reflex resulting from ARH stimulation.