AbstractThe glutamatergic pyramidal cell (PYR) to pyramidal cell synapse was compared to the PYR to inhibitory interneuron (INT) synapse in area CA3 of rat hippocampal roller‐tube cultures. Paired‐pulses and tetanic stimulations of a presynaptic PYR were conducted utilizing dual whole‐cell patch‐clamp recordings of either two PYRs or of a PYR and visually identified stratum oriens INT. Differences in synaptic characteristics were observed, depending on the postsynaptic target cell. Across cell pairs the variation of EPSC amplitudes was much larger for postsynaptic PYRs than for INTs. EPSCs recorded from INTs had faster rise times and shorter decays than those recorded in PYRs. There were also differences in the short‐term plasticity of these synapses. Dual PYR:PYR recordings during paired‐pulse stimulation at 100 ms interstimulus intervals demonstrated no modulation of EPSC amplitudes, while PYR:INT synapses showed paired‐pulse depression. During trains of action potentials, the PYR:PYR EPSCs followed the presynaptic action potential train reliably, with little depression of EPSCs, while PYR:INT EPSCs demonstrated failures of transmission or profound depression after the initial EPSC. These results indicate multiple differences at both the pre‐ and postsynaptic level in the characteristics of pyramidal cell synapses that depend on the postsynaptic target's identity as either PYR or INT. Synapse 42:199–202, 2001. © 2001 Wiley‐Liss, Inc.