Using 133Xe regional cerebral blood flow (CBF) imaging, two male groups having high and low hypnotic susceptibility were compared in waking and after hypnotic induction, while at rest and while experiencing ischemic pain to both arms under two conditions: attend to pain and suggested analgesia. Differences between low and highly-hypnotizable persons were observed during all hypnosis conditions: only highly-hypnotizable persons showed a significant increase in overall CBF, suggesting that hypnosis requires cognitive effort. As anticipated, ischemic pain produced CBF increases in the somatosensory region. Of major theoretical interest is a highly-significant bilateral CBF activation of the orbito-frontal cortex in the highly-hypnotizable group only during hypnotic analgesia. During hypnotic analgesia, highly-hypnotizable persons showed CBF increase over the somatosensory cortex, while low-hypnotizable persons showed decreases. Research is supportive of a neuropsychophysiological model of hypnosis (Crawford, 1991; Crawford and Gruzelier, 1992) and suggests that hypnotic analgesia involves the supervisory, attentional control system of the far-frontal cortex in a topographically specific inhibitory feedback circuit that cooperates in the regulation of thalamocortical activities.