The neural mechanisms underlying the antinociceptive effects of hypnosis are not well understood. Using positron emission tomography (PET), we recently showed that the activity in the anterior cingulate cortex (midcingulate area 24a') covaries with the hypnosis-induced reduction of affective and sensory responses to noxious thermal stimulation [Faymonville et al., Anesthesiology 92 (2000) 1257-1267]. In the present study, we assessed changes in cerebral functional connectivity related to the hypnotic state, compared to simple distraction and the resting state. Nineteen highly hypnotizable right-handed volunteers were studied using H2(15)O-PET. The experimental conditions were hot noxious or warm non-noxious stimulation of the right hand during resting state, mental imagery and hypnotic state. Using a psychophysiological interaction analysis, we identified brain areas that would respond to noxious stimulations under the modulatory action of the midcingulate cortex in, and only in, the hypnotic state. Hypnosis, compared to the resting state, reduced pain perception by 50%. Pain perception during rest and mental imagery was not significantly different. Analysis of PET data showed that the hypnotic state, compared to normal alertness (i.e., rest and mental imagery), significantly enhanced the functional modulation between midcingulate cortex and a large neural network encompassing bilateral insula, pregenual anterior cingulate cortex, pre-supplementary motor area, right prefrontal cortex and striatum, thalamus and brainstem. These findings point to a critical role for the midcingulate cortex in the modulation of a large cortical and subcortical network underlying its influence on sensory, affective, cognitive and behavioral aspects of nociception, in the specific context of hypnosis.