BOLD fMRI was used to study acupuncture-induced activation (increase in the BOLD signal from undetectable) of the periaqueductal gray (PAG) and two somatosensory cortical areas in seven healthy human subjects. Mechanical stimulation (push-pull) was given to the LI4 (Hoku) acupoint or to a non-acupoint. The stimulation paradigm consisted of 5 runs, each consisting of four 30 s On/30 s OFF periods over 30 min. The scan for each ON period was analyzed individually. The PAG and cortical areas showed different activity patterns. PAG activity was episodic and reliably demonstrated after 20-25 min of stimulation; both cortical areas, however, were active > 90% of the time. Stimulation of a non-acupoint (leg) resulted in reduced levels of PAG and cortical activity.