AbstractAlthough interleukin‐1β (IL‐1β) is well known to modulate synaptic transmission and plasticity of the hippocampus, no study has yet evaluated how this cytokine affects long‐term depression (LTD), one of the major forms of hippocampal synaptic plasticity. Here we report that at Schaffer collateral‐CA1 synapses, bath application of IL‐1β induces a long‐lasting decrease in synaptic strength in intact slices, but not in disinhibited slices in the presence of bicuculline, a γ‐aminobutyric acid receptor antagonist. The IL‐1β‐induced synaptic depression efficiently foreclosed the subsequent induction of LTD in response to a 1‐Hz tetanus and, conversely, it was also prevented by preexisting LTD. These results suggest that IL‐1β‐induced, persistent depression of synaptic efficacy is required for GABAergic activation and shares, at least in part, a common cellular mechanism for LTD. Synapse 47:54–57, 2003. © 2002 Wiley‐Liss, Inc.