Transcranial Doppler ultrasonography provides a noninvasive method of predicting stroke risk in children with sickle cell disease. Elevated cerebral blood flow velocity in the terminal internal carotid or middle cerebral artery is associated with an increased stroke risk, but the clinical significance of elevated velocities in the other large intracranial vessels is unknown. The authors report stroke in two children with sickle cell disease and high blood flow velocity limited to the anterior cerebral artery. This suggests that elevated velocity in this vessel may be associated with an increased risk of stroke.