The cerebral metabolic rate for glucose, as measured with positron emission tomography and fluorine-18-labeled 2-deoxy-D-glucose, was significantly higher in four healthy young subjects with trisomy 21 syndrome (Down's syndrome) than the mean rate in healthy young controls. The rate of cerebral glucose utilization in the frontal lobe of a 51-year-old subject with Down's syndrome was significantly lower than the rate in the young subjects with this syndrome, but approximated the rate in middle-aged controls. Thus glucose utilization by the brain appears to be excessive in young adults with Down's syndrome but may decline with age in some brain regions.