The effects of rat interferon (IFN) on the electrically-induced potentiation of the synaptic transmission were studied in rat hippocampal slices by using extracellular field potential recordings. The treatment with rat IFN (120 U/ml) reduced the size of short-term potentiation (STP) and suppressed long-term potentiation (LTP). These IFN-induced effects were dose-dependent in the range of 50-500 U/ml. In addition, IFN slightly attenuated the potentiation when applied during the maintenance of LTP. Basal synaptic transmission was affected by IFN at concentrations greater than or equal to 250 U/ml. Following an acute exposure to IFN (500-200 U/ml), cultured embryonic neurones from rat hippocampus often exhibited an attenuation of N-methyl-D-aspartate-induced currents and a variation (increase or decrease) of voltage-activated Ca2+ current amplitude. A possible role of IFN as neuromodulator in mammalian brain during immune responses is discussed.