Inadequate analgesia or anxiety may induce an increased stress response in patients undergoing carotid endarterectomy (CEA) under regional anesthesia (RA). Central alpha2 adrenoceptor agonists have significant sedative and analgesic properties, which may attenuate sympathoadrenal activation during CEA and improve the quality of RA. We randomly assigned 80 patients to 2 groups receiving either RA plus placebo (n = 40) or RA plus clonidine 1 microg/kg as the initial loading dose followed by 1 microg.kg(-1).h(-1) (n = 40). RA was performed as combined deep and superficial cervical plexus blockade. Hemodynamic and neurological variables were assessed before, during, and after CEA. Arterial blood samples were collected at defined time points for the determination of plasma concentrations of epinephrine, norepinephrine, cortisol, and creatinine kinase and creatinine kinase-MB. Throughout the study, all patients responded easily to neurological evaluations. Before and during clamping mean arterial blood pressure and heart rate were not different between the groups, but mean arterial blood pressure was lower in the clonidine group (P < 0.01) at skin closure and postoperatively in the intensive care unit. In the placebo group, cortisol, epinephrine, and norepinephrine plasma concentrations were increased significantly (P < 0.05) and more patients required antihypertensive treatment (P < 0.01). Postoperatively the incidence of hypertension (P < 0.001) and development of neurological deficits (P < 0.05) was significantly decreased in the clonidine group. We conclude that 1 microg.kg(-1).h(-1) clonidine suppresses the hyperadrenergic response to CEA without adverse effects on hemodynamics or clinical neurological monitoring.