SUMMARY1. The effects of metabotropic glutamate receptor agonists on excitatory synaptic transmission in the CAI region of rat hippocampal slices (11-30 days) were studied using extracellular and whole-cell patch-clamp recording techniques.2. Trans-1-amino-1,3-cyclopentanedicarboxylic acid (trans-ACPD; 25-100 ,sM) reversibly depressed excitatory postsynaptic currents (EPSCs) without affecting presynaptic fibre excitability or EPSC reversal potential.3. Ibotenate (25 ,lM) or L-glutamate (250 /1M), in the presence of the N-methyl-Daspartate (NMDA) receptor antagonist, D-2-amino-5-phosphonovaleric acid (APV, 50-75 JLM), depressed the EPSC amplitude while inducing no detectable inward current. L-2-Amino-4-phosphonobutyrate (L-AP4, 25-100 /tM), the phosphonic derivative of glutamate, also depressed EPSC amplitude and caused no detectable inward current.4. The NMDA receptor-mediated component of the EPSC recorded in the presence of the non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 20-30 ,tM) was depressed by trans-ACPD, L-AP4, or quisqualate (1-2 /,M).5. The response to ionophoretic application of a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) was unaffected by trans-ACPD or L-AP4 although the simultaneously recorded EPSC was strongly depressed. In addition, paired-pulse facilitation (50-75 ms interstimulus interval) was reversibly enhanced by trans-ACPD or L-AP4. These results indicate that the depression of synaptic transmission likely was mediated by a presynaptic 'autoreceptor'.6. The effects of trans-ACPD or L-AP4 on synaptic transmission decreased significantly over ages 12-30 days and were minimal in adult ( > 80 days) slices.7. The depression of synaptic transmission caused by trans-ACPD or L-AP4 was not altered following the induction of long-term potentiation (LTP).