Kynurenic acid, a tryptophan metabolite, inhibits excitatory synaptic transmission in the rat hippocampal slice and the isolated immature rat spinal cord, but does not affect membrane potential or input resistance of hippocampal CA1 pyramidal cells. Kynurenic acid also antagonizes responses induced in the dentate gyrus by excitatory amino acids, particularly N-methyl-DL-aspartate and the endogenous excitant quinolinic acid. These results indicate that kynurenic acid antagonizes synaptic transmission probably by blocking postsynaptic transmitter receptors at putative amino acid mediated synapses.