Although ketone metabolism is generally believed to be qualitatively similar to glucose consumption in the human brain, this has never been explicitly determined. We used 13C-MR spectroscopy with infusions of 13C-[2,4]-b-hydroxybutyrate (BHB, 200 mm, 100% enrichment) in overnight fasted adult subjects (n = 4) to examine the fate of this ketone. This was performed on a 2.1T Bruker spectrometer, volume size 6 × 4 × 6 cc3, previously determined to contain ∼ 56% gray, 39% white matter in normal adults. Results: The 2 h infusion increased plasma ketone levels from near negligible (baseline) to 2.25 ± 0.24 mm at steady state. Steady state 13C BHB levels were measured at 0.18 ± 0.04 mm. Similar to glucose, the 13C label appeared rapidly in the amino acid pools. The steady state fractional enrichment reached were: 13C-4-glutamate (4-Glu), 6.78 ± 1.71%, 13C-4-glutamine (4-Gln), 5.68 ± 1.84 and 13C-3-aspartate at 3.99 ± 0.57%. Discussion: The relatively low [BHB] of 0.18 ± 0.04 mm is an upper bound for tissue BHB, and is in agreement with the view that ketone consumption is largely regulated at the blood brain barrier in these nonfasted acutely hyperketonemic subjects. The general pattern of labeling of ketones is similar to that which has been previously seen with glucose. Steady state analysis of the ratio of 4-Gln/4-Glu suggests that ketones are predominantly used by neurons, and are consumed at a rate of 0.032 ± 0.009 mm/kg/min. This rate includes gray and white matter consumption. Dynamic modelling of the time courses of the brain 4-Glu and 13C-BHB, where gray matter ketone consumption is taken as three times greater than white matter (similar to that seen with glucose) gives an estimated upper bound for the flux of ketone oxidation in pure gray matter to be 0.041 ± 0.007 mm/kg/min.