The aim of this study was to evaluate the effects of intravenous fentanyl and local lidocaine infiltration on the hemodynamic response to Mayfield skull pin head holder (MH) placement. Forty-five patients scheduled for elective craniotomy were studied. They were randomly divided into three groups. Group F received fentanyl 2 μg/kg IV 5 min before placement of the MH, group L was administered plain lidocaine 3 ml 1% by infiltration at each pin site 1 minute before placement, and both methods were applied together in group FL. Mean blood pressure (MAP) and heart rate (HR) were recorded at 5 preset times. In group F during and after MH placement, MAP and HR were significantly higher than in the L and FL groups. In the L group, there was significantly higher MAP and HR during the placement of MH than in the FL group. In the FL group, there was no significant increase in MAP or HR at any time of the recordings. We conclude that intravenous fentanyl with local infiltration of lidocaine into the periosteum is effective in reducing the hemodynamic response to MH placement in patients undergoing craniotomy.