The neuronal protein S-100B has been found to be an indicator of cellular brain damage. The aim of the study was to evaluate whether cross-clamping of the carotid artery for carotid endarterectomy (CEA) under local anesthesia is associated with the same S-100B release pattern as during general anesthesia, where an increase in S-100B concentration in the jugular vein blood of 120% has been reported. In 45 consecutive patients undergoing CEA under local anesthesia, serum S-100B samples were drawn before surgery (T1), before carotid cross-clamping (T2), before cerebral reperfusion (T3), after reperfusion but before the end of surgery (T4), and 6 hr postoperatively (T5). At T1 and T5, blood samples were drawn only from the radial artery. Intraoperatively (T2-T4), samples were collected from the internal jugular vein additionally. S-100B levels were determined using an immunoluminometric assay (LIAISON) Sangtec 100; Sangtec, Bromma, Sweden). In eight patients, it was necessary to insert an intraluminal shunt because of signs of cerebral ischemia. In the remaining 37 patients, median carotid clamping time was 40 min. There were no neurological complications. There were no differences in baseline S-100B levels regarding gender and symptomatology. Median baseline (T1) and postoperative (T5) S-100B levels were identical (0.077 microg/L). All blood samples from the jugular vein showed significantly higher median S-100B levels than the corresponding arterial blood samples. Only slight increases of 13% and 18% were found during cross-clamping (T3) compared to the first intraoperative measurement (T2) in the venous and arterial samples, respectively, which was followed by decreases of 5% and 18%, respectively (T3-T4). S-100B release did not differ at any time point between patients who needed and patients who did not need a shunt, in either the arterial or the venous blood samples. During uncomplicated CEA under local anesthesia, there is no relevant increase of S-100B. These results are different from those reported when CEA is done under general anesthesia.