Astrocytes appear to be ideally localized to couple neuronal activity to energy metabolism. First, specialized processes, the astrocytic end-feet surround blood vessels, the source of glucose for the brain. Second, other processes ensheath synapses and express receptors and transporters for various neurotransmitters, endowing astrocytes with the capacity to 'sense' synaptic activity. We have previously described the stimulation by L-glutamate of glucose utilization by astrocytes, monitored by 2-deoxyglucose uptake and phosphorylation. Here we have further characterized the pharmacological characteristics and molecular mechanisms of this action, which involve a massive influx of Na+ as a result of the cotransport of the amino acid with Na+, by Na(+)-dependent transporters and a subsequent activation of the Na+/K+ ATPase. To fuel the ATPase, glucose is processed glycolytically thus leading to increased lactate production. Since excitatory amino acids are released during activation by cortical afferents, these data reveal a simple mechanism for coupling neuronal activity to glucose utilization and provide further evidence for the concept of a transient stimulation of aerobic glycolysis during activation occurring preferentially in astrocytes.