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Interleukin-1 (IL-1) exerts numerous effects in the central nervous system and has been implicated in synaptic plasticity. The objective of this study was to investigate the role of endogenous as well as exogenous IL-1 on long-term potentiation (LTP). Hippocampal slices incubated at 34–36 °C show enhanced levels of IL-1α and IL-1β compared to slices incubated at 21–24 °C. IL-1 inhibits LTP induced by theta-burst stimulation (TBS) at either temperature. IL-1 receptor antagonist (IL-1ra) had no effect on LTP at 21–24 °C, but displayed a concentration-dependent inhibition of LTP at 34–36 °C. Under control conditions, the magnitude of LTP was not temperature dependent. These data suggest that IL-1 is required for LTP under physiological conditions but at higher doses, as encountered in pathological conditions, IL-1 inhibits LTP.