Direct experimental evidence in support of the method employing radioactive 15O-tagged Hb for the in vivo and regional measurement of the cerebral O2 utilization rate (CMRO2) was sought. This was done by simultaneously measuring in vivo the mean CMRO2 in monkeys [Macaca mulatta] and human beings by the 15O method and a direct appeal to the Fick principle using measured arteriovenous O2 differences of brain. The correlation between the 2 methods was excellent, with a correlation coefficient of 0.90 (P < 0.001) in monkeys and 0.88 (P < 0.001) in human beings.