The defense reaction, a fundamental reflex in the human behavioral response to threat, is characterized by anxiety and increased activity of the sympathetic nervous system. To study changes in regional cerebral blood flow (rCBF) related to the defense reaction, volunteers with snake phobia were investigated with positron emission tomography. The relative rCBF during phobogenic visual stimulation was increased in the secondary visual cortex but reduced in the hippocampus, orbitofrontal, prefrontal, temporopolar, and posterior cingulate cortex compared with that observed during neutral visual stimulation. The relative rCBF under aversive stimulation was intermediate between phobic and neutral stimulation. The rCBF patterns observed are suggested to represent a functional cerebral correlate to the visually elicited defense reaction and its associated emotions.