The purpose of this study was to explore whether the changes of plasma concentrations of endothelin (ET) and calcitonin gene-related peptide (CGRP) were possibly involved during desflurane anesthesia in patients undergoing intracranial aneurysm clipping. Forty-five consecutive patients scheduled for selective craniotomy and aneurysm clipping were anesthetized with desflurane in oxygen. Radial arterial catheter was inserted for blood sampling before anesthesia. Serial plasma concentrations of ET and CGRP were measured with radioimmunoassay prior to induction, after dura incision, after clipping of the aneurysm, and 30 minutes after clipping the aneurysm, respectively. Plasma concentrations of ET decreased significantly during the anesthesia and surgery compared with the baseline. An observed decrease in mean CGRP during anesthesia and surgery was not statistically significant. Considering the well-recognized vasoconstrictive effect of ET, it is possible that a decrease in its plasma concentration plays a role in the prevention of the acute cerebral vasospasm during desflurane anesthesia in patients undergoing intracranial aneurysm clipping.