Excitatory synaptic transmission was decreased in the presence of trans-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD) during whole-cell recordings from striatal slices. This effect of t-ACPD increased in a concentration-dependent manner at drug concentrations from 5-100 microM. Decreased transmission appeared to result from a presynaptic effect as indicated by the observations that: (1) t-ACPD decreased the amplitude of excitatory postsynaptic potentials (EPSPs) mediated by either quisqualate alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) or N-methyl-D-aspartate (NMDA) receptors, but did not block responses to agonist application; indicating that t-ACPD is not a glutamate receptor antagonist; (2) t-ACPD decreased transmission in the absence of changes in postsynaptic cell properties. The t-ACPD-activated receptor appears to differ from previously identified presynaptic receptors. These findings indicate that t-ACPD activates a presynaptic receptor; most likely a glutamate receptor.