Baclofen, a selective agonist at the gamma-aminobutyric acidB (GABAB) receptor, has been considered to reduce the release of transmitter from nerve terminals by acting on presynaptic GABAB receptors, in addition to its postsynaptic action. The purpose of this study has been to re-examine quantitatively the action of baclofen in the hippocampus by a rigorous quantal analysis. (+/-)-Baclofen suppressed field potentials and intracellularly-recorded synaptic potentials induced in the subfield CA3 by mossy fiber stimulation in thin transverse sections of the guinea pig hippocampus. The amplitude distribution of excitatory postsynaptic potentials (EPSPs) induced monosynaptically by a granule cell could be described by the Pascal statistics. Suppression of the unitary EPSPs by baclofen (1 and 5 microM) was accompanied by decreases both in mean quantal content (m) and by mean quantal amplitude (q). The reduction in q was smaller than expected from a decrease in the input resistance of the postsynaptic neuron. It was suggested that the presynaptic and postsynaptic actions of baclofen contribute almost equally to suppression of the transmission at 1 microM, whereas the presynaptic action predominates at 5 microM.