We had previously reported that plasma concentrations of endothelin (ET) decreased significantly in the operating room during desflurane anesthesia. The purpose of the present Study was to explore whether changes in plasma ET and calcitonin gene-related peptide (CGPP) concentrations were altered during propofol anesthesia in patients undergoing clipping of an intracranial aneurysm. Forty-five patients scheduled for selective craniotomy and aneurysm clipping were anesthetized with propofol. A catheter was inserted into the radial artery for blood sampling before anesthesia. Serial plasma concentrations of ET and CGRP were determined before induction, after dura incision, after clipping of the aneurysm, and 30 minutes after clipping. ET concentrations in the plasma increased significantly after clipping of the aneurysm compared with concentrations after dura incision. However, no significant changes in ET levels were found after anesthesia. Plasma concentrations of CGRP decreased significantly during anesthesia. This evidence suggests that direct stimulation of the intracalvarium blood vessel before aneurysm clipping may increase ET; however, propofol did not decrease ET, in contrast with our previously reported findings for desflurane anesthesia. Considering the well-recognized vasodilatory effect of CGRP, it is possible that a decrease in the plasma concentration of CGRP plays a role in the pathogenesis of cerebral vasospasm, which is often seen postoperatively.