The mechanisms by which cognitive processes influence states of bodily arousal are important for understanding the pathogenesis and maintenance of stress-related morbidity. We used PET to investigate cerebral activity relating to the cognitively driven modulation of sympathetic activity. Subjects were trained to perform a biofeedback relaxation exercise that reflected electrodermal activity and were subsequently scanned performing repetitions of four tasks: biofeedback relaxation, relaxation without biofeedback and two corresponding control conditions in which the subjects were instructed not to relax. Relaxation was associated with significant increases in left anterior cingulate and globus pallidus activity, whereas no significant increases in activity were associated with biofeedback compared with random feedback. The interaction between biofeedback and relaxation, highlighting activity unique to biofeedback relaxation, was associated with enhanced anterior cingulate and cerebellar vermal activity. These data implicate the anterior cingulate cortex in the intentional modulation of bodily arousal and suggest a functional neuroanatomy of how cognitive states are integrated with bodily responses. The findings have potential implications for a mechanistic account of how therapeutic interventions, such as relaxation training in stress-related disorders, mediate their effects.