Pial arteriolar caliber and responsiveness were studied using two preparations, the cranial window technique, in which the integrity of the skull is preserved, and an open skull preparation, in which the surface of the brain was covered with stagnant CSF with or without an overlying layer of mineral oil. For the vessel size range studied (30-300 μm in diameter), vessel diameter using either oil or artificial CSF in the open preparation was 20% less than the diameter of the same vessels using the cranial window filled with artificial CSF (P < 0.01). At a constant PaCO2, the pH of the artificial CSF in the open preparation rose from 7.35 to 7.9 to 8.1 in 10 min due to loss of carbon dioxide from the CSF into the air, but the pH of the CSF in the closed system of the cranial window remained constant. The small difference in the extravascular pressure (5 mm Hg) in the two preparations was found not to affect the resting vessel diameter and responsiveness of the vessels. The vasodilation in response to arterial hypercapnia was more pronounced and the vasoconstriction in response to arterial hypocapnia was less pronounced in the open preparation than when the cranial window was used. Small pial arterioles responded to norepinephrine with dose-dependent vasoconstriction in the open preparation, while they showed no significant change in caliber in the cranial window preparation. The responsiveness of vessel caliber to induced hypotension was not different in the two preparations. These results show that in the open preparation CSF pH is abnormally high due to loss of CO2 from the exposed surface of the brain. This results in arteriolar vasoconstriction and in significant alteration in the responsiveness of the vessels to some stimuli. © 1978.