“New” glucose production has been measured in 54 infants and children for the first time by continuous three-to-four-hour infusion of the safe, nonradioactive tracer 6,6-dideuterogiucose. The use of combined gas chromatography-mass spectrometry with monitoring of selected ions allowed deuterium enrichment in blood glucose to be measured on microliter samples with an error of less than 2 per cent. In the young child, glucose production increased in a slightly curvilinear manner from 1 kg. to 25 kg. body weight, when it reached 140 mg. per minute, almost the adult value of 173 mg. per minute (2.28 ± 0.23 mg./kg. ·min., mean ± S.E.). Normalized for weight, glucose production in premature infants was 5.46 ± 0.31 mg./kg. ·min., in term neonates averaged 6.07 ± 0.46 mg./kg. · min., in children below the age of six years was 7.1 ± 0.27 mg./kg.· min., and in late childhood averaged 5.4 ± 0.28 mg./ kg.· min. Relative to estimated brain weight, however, glucose production was essentially linear from the 1-kg. premature infant to the 80-kg. adult. These data, the first measurements of “new” glucose production in childhood, suggest that brain size may be a principal determinant of those factors that regulate hepatic glucose output throughout life.