BACKGROUND After experimental carotid sinus denervation in animals, blood pressure (BP) level and variability increase markedly but normalize to preoperative levels within 10 to 14 days. We investigated the course of arterial BP level and variability after bilateral denervation of the carotid sinus baroreceptors in humans. RESULTS We studied 4 women (age 41 to 63 years) who were referred for evaluation of arterial baroreflex function because of clinical suspicion of carotid sinus denervation attributable to bilateral carotid body tumor resection. The course of BP level and variability was assessed from repeated office and 24-hour ambulatory measurements (Spacelabs/Portapres) during 1 to 10 years of (retrospective) follow-up. Rapid cardiovascular reflex adjustments to active standing and Valsalva's maneuver were assessed. Office BP level increased from 132/86 mm Hg (range, 118 to 148/80 to 92 mm Hg) before bilateral surgery to 160/105 mm Hg (range, 143 to 194/90 to 116 mm Hg) 1 to 10 years after surgery. During continuous 24-hour noninvasive BP recording (Portapres), a marked BP variability was apparent in all 4 patients. Initial symptomatic hypotension on change to the upright posture and abnormal responses to Valsalva's maneuver were observed. CONCLUSIONS Acute carotid sinus denervation, as a result of bilateral carotid body tumor resection, has a long-term effect on the level, variability, and rapid reflex control of arterial BP. Therefore, in contrast to earlier experimental observations, the compensatory ability of the baroreceptor areas outside the carotid sinus seems to be of limited importance in the regulation of BP in humans.