Several studies suggest that relative changes in cerebral blood flow (CBF) may be assessed via transcranial Doppler sonography (TCD). The present study investigates the correlation between changes in TCD-mean flow velocity (Vm) and changes in CBF in patients with a variety of types of intracranial pathology undergoing cerebrovascular reactivity tests. After informed consent was obtained, 32 patients presenting with stenoses of brain-supplying arteries (n = 13), cerebral vascular malformations (n = 6), surgical decompression for subarachnoid hemorrhage (n = 2), brain edema after closed head injury (n = 8), or hepatic encephalopathy (n = 3) were studied. The patients were divided into two groups for different reactivity tests. Patients in group 1 (awake or sedated, n = 18) received a 1-g dose of acetazolamide intravenously. In group 2 (n = 14), mechanical ventilation was adjusted to produce a 20% decrease in arterial CO2 tension compared with baseline. Regional CBF was measured using xenon-enhanced computed tomography (Xe-CT). Xe-CT scans at the levels of the basal ganglia and the lateral ventricles were performed during a 4.5-min xenon wash-in period. Bilateral flow velocity was measured in the middle cerebral artery using a 2-MHz pulsed TCD system. Mean arterial blood pressure, heart rate, and end-tidal CO2 were continuously recorded during the procedure. After baseline measurements and either alteration of CO2 or application of acetazolamide, the cerebrovascular reactivity was assessed at 20 min by a second measurement of CBF, TCD, and all other physiologic variables. The correlation coefficient for relative changes of MCA territory CBF versus Vm and for the overall population was r = 0.82. In groups 1 and 2, the r values were 0.39 and 0.5, respectively. Correlation coefficients did not exceed r = 0.4 in any subgroup-classification based on diagnosis. The close correlation between changes in CBF and Vm (r = 0.82) in patients with heterogeneous intracranial pathology seems to show that TCD is a measure of CBF. However, in groups 1 and 2 and in subgroups formed of patients classified according to diagnoses, data dispersion suggests that the actual correlation is weaker. Relation of changes in Vm to those in CBF may depend on the underlying diagnosis. These data indicate that the correlation between Vm and CBF may vary with intracranial pathology.