The brain has one of the highest metabolic rates of any organ in the body. Any perturbation of the metabolism of the brain has serious negative effects on the well-being and survival of the organism. The contribution of various different cell-types in the brain to overall metabolism cannot be determined by in vivo experiments. Growth of these sub populations separately in tissue culture permits examination of the metabolism of each individually. Furthermore, the effect of stimulation or inhibition of brain metabolism can be assessed on the separate cell populations. Results from such studies demonstrate that neurons and astroglia handle glucose and 2-[14C]DG in a similar fashion under normoglycemic to slightly hyperglycemic (2.0 to 5.0 mM glucose) conditions; the intracellular:extracellular distribution of glucose and 2-[14C]DG is similar in both cell types. However, there appears to be differences between neurons and astroglia in the distribution of glucose under hypoglycemic (0.1 to 0.5 mM glucose) conditions. In vivo, it is during such periods of hypoglycemia that changes in brain cells (particularly neurons) take place that ultimately lead to cell death and tissue damage. Separate studies suggest there is metabolic cooperactivity between these two cell types. One example is CO2 fixation. Only astroglia can fix CO2; this reaction is critical for maintaining the level of substrates in the citric acid cycle. Upon exposure to increased extracellular potassium, the astroglia increase the rate of CO2 fixation into acid-stable products and may export these products to neurons.