We used transcranial Doppler ultrasonography to determine whether intracranial blood velocities in 182 headache-free migraineurs (60 with aura, 122 without aura) differed from velocities in 38 nonheadache prone control subjects. During the headache-free period, migraineurs with and without aura had significantly elevated mean velocities in all intracranial arteries except the right internal carotid artery at the level of the siphon. Velocities in migraineurs with aura did not differ significantly from velocities in those without aura. Markedly increased velocities were noted in a subset of interictal migraineurs. Two explanations are possible: 1) Blood flow velocities may increase in response to a decrease in the cross sectional area of a vessel at or near the point of insonation. 2) Alterations at the level of the cerebral arteriole may affect regional cerebral blood flow, thereby changing blood flow velocities at the point of insonation. Transcranial Doppler sonography alone cannot sort out which process is responsible for the vascular response. This work may have therapeutic as well as diagnostic implications. When interictal flow velocities are markedly increased, it is possible that therapeutic agents with vasoconstrictor action might cause an excessive response. Further study is needed to clarify the sites of vasoreactivity as well as the magnitude of drug-induced vasoconstrictor response.