2-Deoxyglucose (2DG) studies have been most useful in mapping activated regions of the nervous system. Cellular localization studies using 2DG have been less rewarding, but results are consistent with current views that increases of 2DG accumulation produced by synaptic activation represent increases in glycolytic glucose metabolism occurring mainly in presynaptic neuronal and possibly glial elements. Immediate early genes (IEGs), including the fos, jun, and NGFI-A families, are induced by a wide variety of intracellular signaling pathways. The nuclear localization of the protein products of these genes and their induction by a variety of stimuli make them useful in metabolic activation studies carried out at the cellular level. IEGs have been induced in neurons by osmotic, bacterial endotoxin, steroids, stress, and other hormonal stimuli; by light, auditory, painful, and other sensory stimuli; during stimulation of motor cortex and other motor behaviors; and by various drugs and toxins that act on a variety of neurotransmitter systems, including dopamine and glutamate. In addition, the localization of c-fos gene expression identifies cells that respond to growth factors in vivo. Retinal Muller cells, the major glial cell type of the retina, demonstrate nuclear Fos immunostaining after the intravitreal injection of epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha). This observation demonstrates that adult glia can respond to these growth factors in vivo. The investigation of early response gene expression may be particularly useful for elucidating the role of trophic factors in the cellular response to central nervous system injury.