We tested dexmedetomidine, an alpha2 agonist, for its ability to decrease heart rate, arterial blood pressure, and neuroendocrinal responses to skull-pin head-holder application during craniotomy. In a randomized, double-blinded, placebo-controlled study, 40 patients undergoing craniotomy with attachment of a pin head-holder were randomly assigned to one of 2 equal groups. The placebo group received saline, whereas the treatment group (DEX group) received a single bolus dose of dexmedetomidine (1 microg/kg) intravenously over 10 minutes before induction of anesthesia. Arterial blood pressure, heart rate, and sequential concentrations of circulating cortisol, prolactin, insulin, and blood glucose were measured. Relative to baseline and the other group, arterial blood pressure and heart rate decreased significantly after the administration of dexmedetomidine through skull pinning (P<0.05). In the placebo group, patients' heart rate and arterial blood pressure measures increased at 1 and 5 minutes after skull-pin insertion, compared with baseline and the DEX group (P<0.05). In both groups, plasma cortisol, prolactin, and blood glucose increased significantly relative to baseline after skull-pin insertion. However, the values were significantly higher in the placebo group compared with the DEX group (P<0.05). Although insulin levels were not significantly altered in the DEX group, the plasma concentrations of insulin decreased significantly after pin insertion in the placebo group. Our results suggested that, a single bolus dose of dexmedetomidine before induction of anesthesia attenuated the hemodynamic and neuroendocrinal responses to skull-pin insertion in patients undergoing craniotomy.