OBJECTIVE Testing autoregulation is of importance in predicting risk of stroke and managing patients with occlusive carotid arterial disease. The use of small spontaneous changes in arterial blood pressure and transcranial Doppler (TCD) flow velocity can be used to assess autoregulation noninvasively without the need for a cerebrovascular challenge. We have previously described an index (called "Mx") that achieves this. Negative or low positive values (<0.4) indicate intact pressure autoregulation, whereas an Mx greater than 0.4 indicates diminished autoregulation. The objective of this study was to compare acetazolamide reactivity of positron emission tomography (PET)-derived cerebral blood flow (CBF) with Mx in patients with carotid arterial disease. METHODS In 40 patients with carotid arterial disease, we used bilateral TCD recordings of the middle cerebral artery to derive Mx and compared this with PET-derived CBF measurements of acetazolamide reactivity. RESULTS Mx correlated inversely with baseline PET CBF (P = 0.042, R = -0.349) but not with postacetazolamide CBF or cerebrovascular reactivity to acetazolamide. This may reflect discordance between pressure autoregulation and acetazolamide reactivity. Mx correlated significantly with degree of internal carotid artery stenosis (P = 0.022, R = 0.38), whereas CBF reactivity to acetazolamide did not correlate with Mx (P = 0.22). After the administration of acetazolamide, slow-wave activity in blood pressure and TCD flow velocity recordings was seen to diminish, rendering the calculation of Mx unreliable after acetazolamide. CONCLUSIONS The measurement of Mx offers a noninvasive, safe technique for assessing abnormalities of pressure autoregulation in patients with carotid arterial disease.