Here we present the first demonstration that 2-deoxy-2[18F]fluoro-D-glucose (18FDG) and micro Positron Emission Tomography (μPET) can be used successfully to monitor regional changes in brain metabolism during acute seizure induction in C57Bl/6 mice. These longitudinal studies show a significant increase in 18FDG uptake in the hippocampus (33.2%) which correlates directly with seizure severity (R2 = 0.86). 18FDG μPET can potentially be used to monitor the development of TLE in mouse models from the acute phase of status epilepticus to the chronic phase of spontaneous recurrent seizures. These studies provide a foundation upon which we can begin to identify genetic contributions to the metabolic signature of TLE in mice, since many transgenics are in the C57Bl/6 background strain. Synapse 59: 119–121, 2006. © 2005 Wiley-Liss, Inc.