GABAA receptors respond to the local release of GABA from presynaptic terminals. In addition, extracellular GABA can tonically activate high-affinity, extrasynaptic GABAA receptors (GABAAR). Specific GABAAR subtypes have been proposed to mediate this current: delta containing receptors in the cerebellum, dentate gyrus and thalamus and alpha5 containing receptors in hippocampal pyramidal cells. Tonic currents are developmentally regulated, depend on synaptic and non-synaptic GABA release and are modulated by GABA uptake. Tonic GABAAR currents play critical roles in regulating network excitability, and information processing. Indeed, recent evidence suggests a role in regulating cognition and memory. In addition, tonic GABAAR currents may determine the firing pattern of thalamocortical neurons. The downregulation of the alpha5 subunit in the hippocampus during epileptogenesis led to the hypothesis that tonic currents are decreased in epilepsy. We have shown that, in epileptic tissue, alpha5-GABAARs are downregulated and no longer contribute to tonic currents. Surprisingly, however, the tonic current is greater in pyramidal cells from epileptic tissue than in pyramidal cells from nonepileptic tissue, implying substitution of alpha5-GABAARs by other GABAA receptor subtypes. The increased tonic current in epilepsy may represent an adaptive mechanism that decreases neuronal excitability, perhaps at the expense of cognitive function.