This investigation tests the hypothesis that the normal cerebral image obtained non-invasively during continuous inhalation of C15O2is related to cerebral blood flow. Trace amounts of CO2labeled with the positron-emitting radionuclide15O were administered to 4 normal subjects at normo- and hypocapnia and to 2 of these subjects at hypercapnia. Hypocapnia typically caused a marked decrease in cerebral15O activity, and hypercapnia a small increase in activity. The relative difference in the change in count rate in response to hypoand hypercapnia is what one would expect if the activity represented blood flow, according to a mathematical model which assumes the15O label enters the brain as water of perfusion. The findings in this study suggest that the normal cerebral image obtained during continuous inhalation of C15O2is related to cerebral blood flow, but in a non-linear fashion, and that the technique would be more sensitive to ischemic events than to hyperemic phenomena.