Mutant epileptic E1 mice are thought to have focal epilepsy of hippocampal origin because glucose utilization is increased in the hippocampus (HPC) during seizures in these mice. However, direct electrographic evidence is still lacking for the notion. We recorded electroencephalograms (EEGs) using depth electrodes in E1 and non-epileptic ddY mice. All the mice were subjected to a conventional seizure-provoking maneuver during EEG recording; each mouse was placed on a mesh floor and observed for 3 min, and then tossed up in the air. When the E1 mice showed signs of abortive seizures or prodromal symptoms including squeaking, running and myoclonus, sporadic spikes or sharp waves were generated exclusively in the HPC. When generalized convulsions followed these prodromes, the sporadic discharges evolved into a burst of generalized spikes which again predominated in the HPC. We also observed the cerebral cortex, amygdaloid, caudate, centro-median thalamic and ventral postero-lateral thalamic nuclei, all of which were found to be only secondarily involved. These findings provide the first electrical evidence that E1 mice have a secondarily generalized seizure that has its initiating focus in the HPC.