Cerebrovascular reactivity to voluntary hyperventilation, moderate hypertension, and physiological activation was studied in nine patients during induced migraine attacks and in four patients between their attacks. Regional cerebral blood flow was measured by the xenon 133 injection technique in 254 areas of one hemisphere. The partly hypoperfused hemisphere allowed for comparison of adjacent hypoperfused and normally perfused brain areas. During attacks the carbon dioxide reactivity was decreased to 2.8 +/- 0.8% per mm Hg in the oligemic regions compared with 5.8 +/- 0.8% per mm Hg in the normally perfused brain. Blood pressure autoregulation was normal in all brain regions. Regional blood flow increase in response to physiological activation was severely impaired in the hypoperfused brain areas, whereas neighboring normally perfused regions reacted normally. Confinement of the regulation abnormalities to the area of the oligemia supports our suggestion that the blood flow changes are caused by a change in local metabolism. Between attacks of migraine, the patients had normal regulation of brain circulation.