GABA_A receptor-mediated signalling in the brain can be divided into phasic inhibition, due to transient activation of synaptic receptors, and tonic inhibition, mediated by persistent activation of extrasynaptic receptors. These two forms of signalling have been proposed to have different roles in information processing (Farrant & Nusser, 2005). We, therefore, asked if these two forms of signalling show distinct voltage dependencies. To address this question, we made whole-cell voltage clamp recordings from CA1 pyramidal cells in hippocampal slices from 3-4 week old rats. All experiments were carried out at 32°C. We isolated the GABA_A receptor-mediated responses by applying ionotropic glutamate receptor and GABA_B receptor antagonists. We measured the holding current during voltage ramps (-70 mV to +40 mV) before and after the application of the GABA_A receptor antagonist picrotoxin (100 µM). We were thus able to determine the voltage dependence of the tonic current. We found that, in contrast to synaptic currents, the tonic current demonstrates significant outward rectification. In addition, the tail but not peak of evoked IPSCs showed similar rectification, consistent with GABA spillover from the synaptic cleft onto extrasynaptic receptors. This rectification could be due to receptor properties or reversal of GABA transporters during depolarisation, leading to GABA accumulation. We therefore repeated the voltage ramp experiments in the presence of GAT-1 and/or GAT-2/3 blockers, SKF-89976A (30 µM) and SNAP-5114 (50 µM), respectively. Block of GABA uptake decreased, but did not abolish, the outward rectification. Rectification index decreased from 4.32±0.65 (control condition, n=11) to 2.85±0.29 (SKF-89976A, n=6, p>0.05) and 1.64±0.19 (SKF-89976A+SNAP-5114, n=3, p<0.05). This result is consistent with a component of the outward rectification being due to reversal of GABA uptake. Alternatively, elevated levels of GABA recruit an additional pool of less rectifying receptors that are otherwise not active under baseline conditions. Perfusing slices with GABA (30-20 µM) in the absence of GAT-1 and GAT-2/3 blockers yielded results similar to those with GABA transporters blocked (rectification index 2.33±0.15, p<0.02 as compared to control, n=9), arguing for the latter possibility. Tonic conductances in CA1 pyramidal cells thus demonstrate marked outward rectification, which is due to receptor properties rather than local GABA accumulation with depolarisation. This outward rectification is likely to act as a homeostatic mechanism increasing tonic inhibition when neurons are depolarised.