Small soluble oligomers of the beta-amyloid peptide (Aβ) are believed to play a central role in the pathology of Alzheimer’s disease. The low-weight aggregates are capable of disrupting synaptic plasticity in the brain and this is thought to contribute to the memory and learning deficits observed in Alzheimer’s Disease. Application of Aβ peptide oligomers to hippocampal slices has previously been demonstrated to block the induction of long-term potentiation (LTP), a form of synaptic plasticity and a model for mechanisms of memory and learning. An understanding of the mechanisms behind the effects of Aβ at hippocampal synapses is crucial if therapeutic intervention in early onset Alzheimer’s disease is to become a realistic option. Aim – to understand how low molecular weight Aβ oligomers influence hippocampal synaptic transmission. Hippocampal slices (400 μm thick) were prepared from adult rats (90-150g) in accordance with Home Office approved procedures, and incubated with a variety of low molecular weight Aβ oligomers. To provide a measure of CA1 excitability field potential EPSPs were recorded from CA1 stratum radiatum with increasing intensity of Schaffer collateral stimulation to generate input-output curves. Pre-incubation of slices with low nM concentrations of synthetic Aβ oligomers increased hippocampal excitability compared with untreated slices. This enhanced excitability in the presence of Aβ was prevented by application of the GABA-A receptor antagonist, picrotoxin, and occluded by the GABA-A receptor agonists taurine (100 μM) and muscimol (2μM). These preliminary results show that low concentrations of Aβ oligomers cause an increase in hippocampal excitability that may arise from interference with fast inhibitory synaptic transmission. Since the concentrations used here are also closer to physiological concentrations than previous studies, our results may indicate an early effect of Aβ oligomers at hippocampal inhibitory synapses in Alzheimer’s disease.