A small decrease in cerebral blood flow (approximately 10%) in response to 100% oxygen (O2) administration is well recognized. This observation was based on human volunteer studies, which employed a nitrous oxide washout method for the measurement of cerebral blood flow. Because this method is now appreciated to be subject to potential errors we have examined the cerebral blood flow response to 100% oxygen using a magnetic resonance imaging technique to quantify changes in carotid and basilar artery flow. The study, was performed in 12 normal male subjects aged 23–42 years. We report decreases in cerebral blood flow ranging from 9 to 31% with a mean value of over 20%. The decrease in cerebral blood flow was greater in seven young subjects (aged 23–26 years) with decreases in cerebral blood flow of 19.3–31.4% (mean 26.8%). In five older subjects (aged 32–42 years), decreases in CBF were smaller (mean 16.2%). The administration of 100% O2 was accompanied by a small decrease in end-tidal CO2 (3.7–7.1%), insufficient to explain the changes in cerebral blood flow. We conclude that the decrease in cerebral blood flow in response to O2 administration is greater than previously described and appears to be greater in young adults.