Abstract 6,7-Dinitro-quinoxaline-2,3-dione (DNQX, FG 9041), a new non-N- methyl- d-aspartate (NMDA) glutamate receptor antagonist, has been reported to block non-NMDA receptor-mediated excitatory amino acidic responses in cultured neurons. We have perfused this compound in vivo through a dialysis fiber placed in the CA1 regions of anesthetized rats to test its effects on CA1 field-evoked potentials. Perfusions of 25–100 μM DNQX completely abolished field excitatory postsynaptic potentials (EPSP) and orthodromic population spikes (PS). This effect was dose-dependent and was reversed after washing with fresh K rebs-Ringer-bicarbonate. Antidromic population spikes and fiber volley potentials were unaffected by perfusions of DNQX up to 100 μM. On the contrary, perfusion of 50 μM d-2-amino-5-phosphonovalerate, a specific NMDA receptor antagonist, left unchanged both field EPSP and orthodromic PS. Results demonstrate that low-frequency transmission at the Schaffer collaterals-CA1 synapse is mediated by non-NMDA glutamate receptors.