The pathophysiological factors of neurogenic or sympathetically mediated essential hypertension are unknown. Neurons close to the surface of the ventrolateral medulla (specifically, in the retro-olivary sulcus [ROS]) are integrally involved in the control of blood pressure by means of efferent connections to presympathetic neurons in the spinal cord. It is hypothesized that vascular contact with the ROS is pathogenically involved in neurogenically mediated hypertension. We evaluated that theory in 20 subjects with uncomplicated stage 1 to stage 2 essential hypertension (EHTN) (18 of whom completed the study). The baseline supine plasma norepinephrine level served as an index of central sympathetic outflow. The response of blood pressure to clonidine was used as a surrogate marker for neurogenically mediated hypertension. We also examined the relationship between those markers and evidence of anatomic abnormalities in the area of the ROS that was provided by magnetic resonance imaging. A vessel contacted the left ROS in 5 of the 18 subjects. Those 5 subjects had higher plasma norepinephrine concentrations than did the 13 subjects without this vascular contact (358 ± 46 versus 76 ± 43 pg/mL, P < 0.001). These 5 subjects also exhibited a significant depressor response to clonidine that tended to be greater than that seen in the 13 subjects without vascular contact (-20.6 ± 3.2 versus - 13.6 ± 9 mm Hg). Both race and baseline mean blood pressure had only an independent effect on the depressor response to clonidine. The findings are consistent with the theory that vascular contact with the left ROS may contribute to neurogenically mediated 'essential' hypertension in some patients.