Dexmedetomidine is a selective α2-agonist approved for sedation of critically ill patients. There is little information on the effects of dexmedetomidine on cerebral blood flow (CBF) or intracranial hemodynamics, despite considerable other pharmacodynamic data. We hypothesized that therapeutic doses of dexmedetomidine would decrease CBF. Therefore, nine supine volunteers, aged 24-48 yr, were infused with a 1 μg/kg IV loading dose of dexmedetomidine, followed by an infusion of 0.2 μg · kg-1 · h-1 (LOW DEX) and 0.6 μg · kg-1 · h-1 (HIGH DEX). Hemodynamic and CBF (via positron emission tomography) measurements were determined at each experimental time point. Dexmedetomidine decreased both cardiac output and heart rate during and 30 min after drug administration. Blood pressure decreased from 12% to 16% during and after the dexmedetomidine administration. Global CBF was decreased significantly from baseline (91 mL · 100 g-1 · min-1 [95% confidence interval, 72-114] to 64 mL · 100 g-1 · min-1 [51-81] LOW DEX and 61 mL · 100 g-1 · min-1 [48-76] HIGH DEX). This decrease in CBF remained constant for at least 30 min after the dexmedetomidine infusion was discontinued, despite the plasma dexmedetomidine concentration decreasing 40% during this same time period (628 pg/mL [524-732] to 380 pg/mL [253-507]).