Cerebrovascular reactivity to CO2 inhalation was studied by transcranial Doppler sonography in 30 patients with classic or common migraine and 39 healthy controls without clinical or ultrasonic signs of arteriosclerosis. Systolic and diastolic Doppler frequencies of the middle cerebral artery were plotted against end-tidal CO2 partial pressure; the reactivity index (I x R) was defined as relative frequency change during a PCO2 increase of 5 mmHg. In the normal subjects, I x R was 20.0 +/- 6.3 for systolic velocities, and 26.0 +/- 8.2 for diastolic values. Migraineurs during their headache-free interval had significantly higher I x R values on the affected side (mean: 41.6 systolic, 61.2 diastolic), compared with either controls (P less than 0.01) or the contralateral side (mean: 28.3 systolic, 30.8 diastolic; P less than 0.01). During the headache attack, CO2 reactivity was significantly lower than normal only for systolic velocities (mean: 8.3; P less than 0.05). Increased CO2 reactivity is thought to be one phenomenon of migraine. Transcranial Doppler CO2 testing of cerebrovascular reactivity is a reliable method that may be of interest for the diagnostic evaluation and management of migraine patients.