We performed a positron emission tomography study, using regional cerebral blood flow as the index of brain activity, to address the specificity of brain activation pattern by acupuncture stimulation of short duration at the classical analgesic point. Needling manipulation at 2 Hz was performed at a classical point of prominent analgesic efficacy (Li 4, Heku) and a near-by non-classical/non-analgesic point, respectively, in normal subjects. Regions activated by acupuncture stimulation at Li 4 included the hypothalamus with an extension to midbrain, the insula, the anterior cingulate cortex, and the cerebellum. Of note, it was only the stimulation at Li 4 that activated the hypothalamus under the similar psychophysical ratings of acupuncture sensation (deqi) as elicited by the stimulation at the two points, respectively. The data suggested that the hypothalamus might characterize the central expression of acupuncture stimulation at the classical analgesic point and serve as one key element in mediating analgesic efficacy of acupuncture stimulation.