Endothelin-1 (ETL-1), a peptide recently isolated from vascular endothelial cells, acts in cerebral arteries in vitro as a potent and long-lasting vasoconstrictor and has been implicated in the development of cerebral vasospasm. To ascertain whether this new vasoconstrictor has any effect on regulation of the cerebral circulation, we measured plasma ETL-1 concentrations in patients undergoing carotid revascularization and attempted to correlate the variations of venous and arterial plasma ETL-1 with the characteristics of the procedure, including cerebral vasospasm. We prospectively studied 11 patients undergoing a total of 14 carotid surgical revascularization procedures (12 endarterectomies, 2 polytetrafluoroethylene bypass grafts from the common to the internal carotid arteries). Before carotid cross-clamping, blood samples were drawn from the internal jugular vein and the healthy common carotid artery proximal to the occlusive lesion to be treated. After endarterectomy, blood samples were withdrawn from the internal, external, and common carotid arteries. After the release of the last clamp, a final aliquot of blood was withdrawn from the internal jugular vein. After plasma extraction on a C2-ethyl microcolumn, plasma endothelin-like immunoreactivity was measured by means of radioimmunoassay with a polyclonal antibody. In 9 of the 11 patients, internal jugular vein ETL-1 concentration decreased statistically significantly after carotid artery cross-clamping (4.2 +/- 1.4 pg/ml vs. 3.9 +/- 1.1 pg/ml; p < 0.05). In the 2 patients in whom ETL-1 levels failed to drop, a shunt was used during the procedure in 1, and the other was the only patient who had an ipsilateral ischemic postoperative stroke. The decrease in internal jugular vein ETL-1 concentration failed to correlate with any of the cross-clamping times. The level of arterial blood ETL-1 remained steady in the common carotid artery before and after cross-clamping (4.5 +/- 1.5 pg/ml vs. 4.6 +/- 0.9 pg/ml). A small, nonsignificant decrease in ETL-1 level was noted in the external and internal carotid arteries after cross-clamping. The decrease in internal jugular vein ETL-1 levels may in part reflect a compensatory response to carotid artery cross-clamping, which could limit the reduction of local cerebral blood flow.