In the cat there is no convincing evidence that a particular compound mediates a supraspinal control of spinal transmission of nociceptive information. There is good evidence that opioid peptides are released segmentally in response to nociceptive input to the spinal cord and that this acts to inhibit motoneurons and to reduce transmission of nociceptive information to supraspinal areas. In the cat there is no evidence that stimulation at supraspinal sites producing analgesia results in a spinal release of opioid peptides. In the rat evidence for the latter has been obtained but there are no data from other species. Tonically present supraspinal inhibition of spinal transmission of nociceptive information in the cat does not involve opioid peptides. Indirect evidence favours a role for 5-hydroxytryptamine and noradrenaline in supraspinal control of spinal processing of nociceptive transmission. Peripheral antagonists of 5-HT have reduced spinal inhibition from stimulation at supraspinal sites but the site of action is unknown. Progress with noradrenaline involvement has been hindered by lack of a suitable antagonist. Although the amino acids, glycine and GABA are involved in segmental inhibition of transmission of nociceptive information, no convincing evidence has indicated their involvement in supraspinal controls.