We sought to evaluate cerebral hemodynamic responses to betel chewing. Thirty healthy male volunteers (mean age = 35 years), ten new chewers, ten occasional chewers, and ten chronic chewers were included in this study. We used carotid duplex sonography and transcranial Doppler to measure the flow velocities and flow volume (FV) of the common carotid (CCA), internal carotid (ICA), external carotid (ECA) arteries, and the flow velocity of middle cerebral artery (MCA). Blood pressure (BP) and heart rate (HR) were recorded simultaneously. All subjects were asked to chew fruit-flavored chewing gum for 10 minutes. Blood flows of the above vessels were measured four times at baseline and at the 2nd, 6th, and 12th minute after chewing. A repeated study was followed in the same subject but substituted with betel nut. Chronic chewers had delayed onset time and shortened vanishing time of facial-flushing sensation. Systolic and diastolic BPs were mildly elevated during gum chewing (p = 0.008 and 0.015, respectively), whereas diastolic BP was dropped during betel chewing (p = 0.008). Heart rate increased prominently during betel chewing (p < 0.0001), especially in new and occasional chewers. The peak systolic, end diastolic velocities, and FV in ECA and CCA increased significantly during betel chewing (p < 0.0001). The blood flows in the ICA and MCA had no significant changes during gum or betel chewing. Betel chewing has a central sympathetic effect resulting in accelerated HR, increased blood flows in ECA and CCA, but has a peripheral cholinergic effect resulting in a drop of diastolic BP. Intracranial cerebral hemodynamics is not affected during betel chewing. The inotropic and chronotropic effect to the heart from betel chewing is probably an unfavorable risk for patients with ischemic heart disease.