Cerebral vasodilator responses to hypercarbia were tested during inhalation of 5% CO2 in air by normal volunteers with and without risk factors for cerebral atherosclerosis. The results were compared with those of patients with hemispheric infarction or ischemia or vertebrobasilar arterial insufficiency (VBI). Regional cerebral blood flow was measured by the 133Xe inhalation method before and during hypercarbia. Responsiveness to CO2 was expressed as the percentage increase of gray matter flow per mm Hg of end-tidal CO2 tension. Cerebral vasodilator responsiveness is mildly impaired by the atherosclerosis of normal aging, is moderately impaired in normal subjects with risk factors for cerebral atherosclerosis, and is greatly impaired in patients with symptomatic hemispheric ischemia and VBI. Testing regional cerebral blood flow with CO2 appears to be a useful, harmless screening test for cerebral atherosclerosis.