There is evidence suggesting that among other factors, an alteration in cerebral hemodynamics plays a relevant role in the occurrence of strokes in patients with carotid disease. The purpose of this study was to investigate patterns of cerebrovascular reactivity in patients with internal carotid occlusion and severe contralateral carotid stenosis and their relationship with symptomatology. Using transcranial Doppler ultrasound, cerebrovascular reactivity to hypercapnia in middle cerebral arteries was evaluated with the breath-holding index (BHI) in 42 patients with internal carotid occlusion and severe contralateral carotid stenosis and in 40 control subjects. A significant decrease of BHI on the occluded side was observed in symptomatic patients with respect to asymptomatic ones (0.12+/-0.1 vs. 0.75+/-0.4, P<0.0001) and with respect to the control group (1.11+/-0.1, P<0.0001). The difference was also significant between asymptomatic patients and controls (P<0.0001). Breath-holding values on the stenotic side were significantly higher (P<0.0001) in asymptomatic patients (1.01+/-0.2) with respect to symptomatic ones (0.39+/-0.1). A significant difference (P<0.0001) was also present between controls and symptomatic patients. The pattern of cerebrovascular reactivity in patients with severe bilateral carotid steno-occlusive disease seems to be strictly dependent on the presence of previous symptoms. Further studies are needed to investigate whether the study of cerebral hemodynamics in patients with bilateral carotid artery disease is important for planning therapeutic strategies.