Systemically administered opioids produce a profound inhibition of noxious-evoked activity peripherally, spinally and supraspinally in several species, including man. The role of the brain in opioid mediated-pain control has been less well characterized than that occurring at lower levels in the nervous system. Yet, classical studies indicate that in morphine-induced analgesia the individual senses noxious stimuli, but the affective, motivational and aversive character of the stimulus is no longer present. This observation indicates that morphine probably exerts a specific action on those brain systems that control complex behaviors like aversion and motivation. The failure to document such effects in experimental studies may in part be explained by less suitable methods for assessing antinociception, e.g. measurements of simple reflex behaviors. Experimental animal studies show that supraspinal opioids may influence nociception by several distinct mechanisms, which differ from those seen in the spinal cord: Change of activity in descending bulbospinal pathways. Direct inhibition of noxious throughput at brainstem level. Indirect inhibition of noxious responding brainstem neurons projecting to supraspinal centers. Influence ascending forebrain systems. Direct cortical or thalamic inhibition. In humans, the antinociceptive actions of opioids occurring in the brain has until recently been like looking into a "black box". The introduction of new imaging techniques may provide new tools for directly measuring the antinociceptive action of opioids in the brain under normal and pathological conditions. In particular, the emotional-affective aspect of pain and how this is modulated by opioids will be of interest to study.