In recent years a vast array of experimental evidence has indicated the presence of functional receptors for neurotransmitters on nonneuronal cells, in particular astrocytes. The two neurotransmitters vasoactive intestinal peptide (VIP) and noradrenaline (NA) exert profound, receptor-mediated, metabolic actions on astrocytes. Thus both neurotransmitters stimulate glycogenolysis in primary astrocyte cultures, with EC50s of 3 and 20 nM respectively. Astrocytes display basal glucose utilization rates ranging between 3 and 9 nmol/mg prot/min, a value that is remarkably close to glucose utilization of cerebral cortical grey matter as determined by the 2-deoxyglucose autoradiographic technique. NA markedly enhances glucose uptake and phosphorylation by astrocytes, with an EC50 of 1 microM. The metabolic substrate that is released by astrocytes is predominantly lactate and not glucose. Since lactate can support neuronal activity and synaptic function in vitro, the possibility should be considered that glucose uptake by the brain parenchyma occurs predominantly into astrocytes which subsequently release lactate for the use of neurons.