The action of interleukin-1 beta (IL-1 beta) and its receptor antagonist IL-1ra were investigated on dual component, isolated AMPA and NMDA field excitatory post-synaptic potentials (EPSP) and on the induction and maintenance of long-term potentiation in the rat dentate gyrus in vitro. Perfusion with IL-1 beta (1 ng/ml) for 1 h had no significant effect on the dual component EPSP or the isolated AMPA-EPSP. In contrast IL-1 beta had a significant inhibitory effect on the isolated NMDA-EPSP amplitude (54 +/- 7% at 1 h compared with controls; n = 9; p < 0.001). This effect was fully antagonized in the presence of 100 ng/ml IL-1 receptor antagonist. IL-1 beta also inhibited LTP of the dual component EPSP but had no effect on the maintenance phase when applied post-induction of LTP. This study demonstrates for the first time that the inhibitory effect of IL-1 beta on LTP in the dentate gyrus may be at least partially due to a block of post-synaptic NMDA receptors.