Pulsatile blood flow within the normal carotid sinus involves at least two distinct components. That near the flow divider is laminar and antegrade, whereas a boundary layer separation zone in the posterolateral aspect exhibits transient blood flow reversal. It is now possible to document these flow velocity components using pulsed Doppler ultrasound methods. When atherosclerosis develops, it preferentially involves the posterolateral bulb region, obliterating the normal configuration of the sinus with consequent loss of the flow separation zone. It was therefore hypothesized that if flow separation could be detected, it should be predictive of a normal angiogram. To assess this, we evaluated 20 symptomatic patients and two with only bruits found by duplex scanning to have flow separation in either one or both carotid bulbs and who also underwent cerebral angiography. Initial diagnoses were stroke in seven, reversible ischemic neurologic deficit in one, transient ischemic attack in 12, and bruit in two. Flow separation was bilateral in 13 patients (59%). There were 15 patients with symptoms in the territory of a carotid bulb exhibiting flow separation. By angiography, of the 35 bulbs with boundary layer separation, 27 (77%) were normal, with the remainder snowing lesions that reduced the diameter of the vessel by 20% or less. Final diagnoses of the 15 patients with symptoms ipsilateral to a carotid sinus exhibiting flow separation were fibromuscular disease in two, lacunar stroke in three, dissection in two, subclavian steal in one, cardiogenic embolus in three, migraine in one, hyperventilation syndrome in one, kink of the mid-internal carotid artery in one, and no diagnosis in one. A normal ultrasound image coupled with flow separation in the carotid bulb in patients presenting with presumptive extracramal carotid disease is therefore shown to be associated with minimal or no carotid atherosclerotic disease on angiography and to reliably predict etiology other than carotid artery disease for the symptoms. (Stroke 1989;20:175-182) C arotid bifurcation disease has been previously quantified by identifying features of blood flow velocity patterns obtained with ultrasound from the proximal internal carotid artery (ICA) and correlating them with the "gold standard" of contrast arteriography.