The effects of NBQX and DNQX on synaptic transmission in rat hippocampal slice were investigated. Both agents produced dose-dependent blockade of field potentials evoked by low frequency stimulation of Schaffer collateral-commissural fibers recorded in medium containing 4 mM Mg2+ (non-NMDA mediated transmission), with half-maximal effects at about 0.15 microM for NBQX and 1.0 microM for DNQX. When the studies were conducted in Mg(2+)-free medium (predominantly NMDA mediated transmission), 100 microM NBQX failed to block transmission; however, the response could be completely blocked by the addition of 10 microM of the competitive NMDA antagonist CPP. In contrast, 47 microM DNQX completely blocked secondary field potentials recorded in Mg(2+)-free medium and this effect could be reversed by the addition of 200 microM of the glycine agonist D-serine. Thus, NBQX exhibited selective blockade of non-NMDA mediated synaptic transmission whereas DNQX had effects at both non-NMDA and NMDA receptor sites, the latter effect via an interaction with the glycine site on the NMDA receptor complex.