Abstract The effects of human recombinant tumor necrosis factor (TNF-α) on the synaptic transmission were studied in rat hippocampal slices by using extracellular field potential recordings. Population spikes and/or excitatory postsynaptic potentials were extracellularly recorded in hippocampus CA1 region from stratum pyramidale and stratum radiatum, respectively, and synaptic transmission was examined in the Schaffer collateral/commissural-CA1 pathway. Basal neurotransmission slightly and promptly increased in slices acutely exposed to TNF-α (1–100 nM). Examination of the long-term potentiation (LTP) revealed that a brief treatment with the cytokine did not influence LTP, while a long-lasting application of TNF-α (50 min or more) inhibited LTP in a dose-dependent way in the range of 1–100 nM. A role for TNF-α as a peptide of immunological significance belonging to the family of brain neuromodulators is discussed.