NMR spectroscopy was used to test recent proposals that the additional energy required for brain activation is provided through nonoxidative glycolysis. Using localized NMR spectroscopic methods, the rate of C4-glutamate isotopic turnover from infused [1-C-13]glucose was measured in the somatosensory cortex of rat brain both at rest and during forepaw stimulation, Analysis of the glutamate turnover data using a mathematical model of cerebral glucose metabolism showed that the tricarboxylic acid cycle flux (V-TCA) increased from 0.49 +/- 0.03 at rest to 1.48 +/- 0.82 mu mol/g/min during stimulation (P < 0.01), The minimum fraction of C4-glutamate derived from C1-glucose was approximate to 75% and this fraction was found in both the resting and stimulated rats, Hence, the percentage increase in oxidative cerebral metabolic rate of glucose use (CMR(gIc)) equals the percentage increases in V-TCA and cerebral metabolic rate of oxygen consumption (CMR(o2)). Comparison with previous work for the same rat model, which measured total CMR(gIc) [Ueki, M., Linn, F. & Hossman, K. A. (1988) J. Cereb. Blood Flow Metab. 8, 486-494], indicates that oxidative CMR(gIc) supplies the majority of energy during sustained brain activation.