BACKGROUND To evaluate the timecourse of cerebrovascular reserve response to breath-holding. METHODS Using simultaneous bilateral transcranial Doppler (TCD) recordings from the MCA during a breath-holding challenge, we measured the time interval between baseline and peak blood flow velocity values in 25 patients with critical unilateral internal carotid artery (ICA) stenosis (> 85% lumen diameter reduction), in 9 patients with a non-critical (70-85%) ICA-stenosis and in 27 normal controls. RESULTS Normal controls and patients with non-critical stenosis reached peak MCA velocities on both sides almost simultaneously. For the patients with critical stenosis the peak response time ipsilateral to the stenosis was delayed 2.40 +/- 3.43 sec compared to the opposite side. This delay resolved after carotid endarterectomy. CONCLUSIONS In response to a breath-holding challenge unilateral critical ICA stenosis is associated with a significant ipsilateral prolongation of the rise time from baseline to peak MCA velocity.