Vasomotor reactivity (VMR) represents the autoregulatory capacity of cerebral vessels and its clinical significance has been reported in steno-occlusive diseases of internal carotid artery (ICA). However, it has yet to be studied in intracranial steno-occlusive diseases. Consecutive patients with middle cerebral artery (MCA) stenosis diagnosed by MR angiography were compared with age-matched controls. Patients with ipsilateral ICA stenosis or advanced small vessel disease were excluded. Degree of stenosis was graded as mild (< 50%), moderate (50-90%), or severe (> 90%). VMR was measured by a semi-closed rebreathing method with monitoring of end-expiratory CO₂ level and calculated by percentage change of mean flow velocity of MCA. Fifty-eight MCAs with stenosis among 44 patients were compared with 38 MCAs without stenosis among 19 controls. VMR was reduced in patients with stenosis as compared with controls (41.6% vs 57.1%, p < 0.001). VMR was more reduced in patients with previous stroke compared with those without previous stroke (27.5% vs 53.1%, p < 0.001). Decrement of VMR was well correlated with degree of stenosis (p < 0.001). Multivariate logistic regression analysis adjusting for age, hypertension and diabetes revealed moderate to severe stenosis as an independent determinant of reduced VMR (odds ratio 10.2, 95% CI 3.35-30.96, p < 0.001). TCD measurement of VMR is feasible in MCA stenosis and VMR is reduced in a dose-responsive manner. These pilot results need to be replicated and further clinical significance of VMR in MCA stenosis remains to be determined. Copyright Â© 2010 Elsevier B.V. All rights reserved.