The electrical activity corresponding to focal human epilepsies usually originates in the cortex, frequently in the temporal lobe. Between seizures, these regions often generate recurring EEG ‘spikes’ – several 10 s or 100 s of milliseconds in duration – termed ‘interictal’ activities. Synaptic, circuit, and cellular mechanisms that underlie such activities are quite well understood; work on animal models, especially in vitro slice preparations, has shown that these spikes reflect synchronized cellular activity. One reasonably well-characterized model for interictal synchrony is the activity induced in acute hippocampal slices by blocking ionotropic receptors for the inhibitory transmitter γ-aminobutyric acid (GABA). Here we describe the circuits responsible for this activity, which is initiated in the CA3 region of the hippocampus. We then confront this model with recent data on interictal-like activities generated by tissue obtained after operations on epileptic patients. Interictal discharges are generated in the subiculum of this human epileptic tissue, where CA3 pyramidal cells are largely lost to sclerosis and depend in part on depolarizing GABAergic signaling.