It is well-known that excitatory synaptic transmission at the hippocampal CA3-CA1 synapse depends on the binding of released glutamate to ionotropic receptors. Here we report that during long-term application of Cs⁺ (5 mM), stimulation of the Schaffer collateral - commisural pathway evokes an epileptic field potential (Cs-FP) in area CA1 of the rat hippocampal slice, which is resistant to antagonists of ionotropic glutamate and GABA_A receptors. The Cs-FP was blocked by N-type but not L-type Ca²⁺-channel antagonists and was attenuated by adenosine (0.5 mM), as expected for a synaptically mediated response. These properties make the Cs-FP fundamentally different from other types of Cs⁺-induced epileptiform activity. Replacement of Cs⁺ with antagonists of the hyperpolarization-activated non-selective cation current I_h and inwardly rectifying potassium channels (K_IR), or partial inhibition of the Na⁺/K⁺-pump did not cause Cs-FP-like potentials, which indicates that such actions of Cs⁺ were not responsible for the Cs-FP. The effect of Cs⁺ was partly mimicked by 4-aminopyridine (4-AP, 2 mM), suggesting that an increase in transmitter release is involved. The group I metabotropic glutamate receptor (mGluR) agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) attenuated the Cs-FP. This effect was not, however, antagonized by group I mGluR antagonists. Selective and non-selective mGluR antagonists did not attenuate the Cs-FP. We conclude that long-term exposure to Cs⁺ induces a state where excitatory synaptic transmission can exist between area CA3 and CA1 in the hippocampus, independent of ionotropic and metabotropic glutamate receptors and GABA_A receptors.