CONTEXT Psychopaths belong to a larger group of persons with antisocial personality disorder and are characterized by an inability to have emotional involvement and by the repeated violation of the rights of others. It was hypothesized that this behavior might be the consequence of deficient fear conditioning. OBJECTIVE To study the cerebral, peripheral, and subjective correlates of fear conditioning in criminal psychopaths and healthy control subjects. DESIGN An aversive differential pavlovian delay conditioning paradigm with slides of neutral faces serving as conditioned and painful pressure as unconditioned stimuli. SETTING The Department of Medical Psychology at the University of Tübingen, Tübingen, Germany. PARTICIPANTS Ten male psychopaths as defined by the Hare Psychopathy Checklist-Revised and 10 age- and education-matched healthy male controls. The psychopaths were criminal offenders on bail and waiting for their trial or were on parole. The healthy controls were recruited from the community. MAIN OUTCOME MEASURES Brain activation based on functional magnetic resonance imaging, electrodermal responses, emotional valence, arousal, and contingency ratings. RESULTS The healthy controls showed enhanced differential activation in the limbic-prefrontal circuit (amygdala, orbitofrontal cortex, insula, and anterior cingulate) during the acquisition of fear and successful verbal and autonomic conditioning. The psychopaths displayed no significant activity in this circuit and failed to show conditioned skin conductance and emotional valence ratings, although contingency and arousal ratings were normal. CONCLUSION This dissociation of emotional and cognitive processing may be the neural basis of the lack of anticipation of aversive events in criminal psychopaths.