Using positron emission tomography (PET) and [15O]butanol we studied regional cerebral blood flow (rCBF) to a visual snake stimulus before and after classical conditioning with an unconditioned electric shock delivered to the right hand. Measures of heart rate, electrodermal activity, state anxiety and subjective distress confirmed classical conditioning of physiological and subjective responses. Subcortically, conditioning increased rCBF bilaterally in the ventromedial thalamus, the posterior hypothalamus and the central grey of the midbrain. Cortically, rCBF increased in the left anterior and posterior cingulate gyrus, the left primary somatosensory cortex, the left premotor cortex and bilaterally in parietal areas. Thus, the functional organization of classical conditioning in humans involves autonomic, affective and attentive brain mechanisms.