The release of the neuronal protein S-100B into the circulation has been suggested as an early indication of cellular brain damage. The objective of this prospective pilot study was to determine S-100B serum levels in patients undergoing cross-clamping during carotid endarterectomy (CEA) and to correlate the results with the monitoring of somatosensory evoked potentials (SSEP) and the neurological short-term outcome. Arterial blood samples of 21 patients were drawn before oral intubation, cross-clamping, and unclamping, as well as before extubation and 6 hours later. Recording of SSEP was obtained during carotid occlusion and reperfusion. If loss of SSEP appeared, cerebral ischemia was assumed and an intraluminal shunt was placed. During cross-clamping, S-100B serum levels of 14 patients increased significantly from 0.05 ng/ml to 0.21 ng/ml, but returned to baseline levels after unclamping. In 5 cases, loss of SSEP amplitudes occurred but was reversed by the shunt insertion. No significant differences of S-100B serum values, neurological examination, and carotid duplex surveillance became obvious in this group when compared to the patients with undisturbed SSEP. However, 2 patients with complete disappearance of postcentral SSEP components suffered from neurological deficits in the postoperative period. S-100B serum levels remained highly elevated 6 hours after extubation (0.78 ng/ml and 0.41 ng/ml) compared to the baseline values (0.15 ng/ml and 0.07 ng/ml). During CEA a transitory increase of the S-100B serum levels appears to present an impairment of the blood-brain barrier integrity without any neurological deficits. In contrast, persistently elevated S-100B serum levels seem to be associated with transient loss of SSEP and development of neurological deficits.