OBJECTIVE Sickle cell disease is associated with cerebral hyperemia, which is therapeutically reduced by transfusion; however, the process of transfusion-induced cerebral perfusion changes has heretofore not been observed. METHODS We document the acute changes of intracranial arterial velocity in 10 patients (7 with strokes, 3 without) undergoing transfusion therapy using transcranial Doppler ultrasonography. Middle cerebral artery velocities were bilaterally measured every 30 minutes for the duration of transfusion (4 to 5 hours). Regional cerebral blood flow was quantified in 5 of these patients before the transfusion and 24 hours later by the 133Xe technique. RESULTS Velocities in stroke-associated vessels (64.33 +/- 18.65 cm/s; n = 6) were significantly lower than in uninfarcted territories (99.54 +/- 27.39 cm/s; n = 13), and both types of vessels showed a robust reduction of blood flow velocities during transfusion. The rates of reduction were not significantly different as a function of prior stroke but did correlate with pretransfusion velocities and with the rise in hematocrit (multiple r = .887, P < .001). These reductions occurred rapidly within the first 3 hours of transfusion. Velocities attained at the end of transfusion were maintained in the hour after transfusion and the next day. CONCLUSIONS We conclude that transfusion induces rapid changes in cerebral hemodynamics that are related to pretransfusion velocities and a rise in hematocrit. Transcranial Doppler provides a safe, simple, and noninvasive technique of monitoring these changes and may provide a means of making therapeutic decisions regarding transfusion therapy in patients with sickle cell anemia.