In the presence of picrotoxin, spontaneous synchronized bursts followed by afterdischarges were recorded from all pyramidal cell regions of the guinea pig hippocampal slice. Excitatory synaptic potentials, which reversed at approx -5 mV, were found to be associated with both the initial burst and each afterdischarge. Afterdischarges were reversibly blocked, leaving the initial synchronized burst intact, by the application of several excitatory amino acid antagonists or by increasing Mg2+ so that the efficacy of synaptic transmission was reduced. All synchronized activity was suppressed by applying an increased concentration of antagonist or by raising Mg2+ and lowering Ca2+ so that synaptic transmission was completely blocked. This synchronized neuronal activity occurred spontaneously in the CA2-3 region when isolated from the CA1 pyramidal cell area and the dentate gyrus. When CA2 was separated from CA3 a synchronized rhythm of single bursts was observed in CA2, while a different, slower, synchronized population discharge consisting of initial bursts followed by afterdischarges occurred in CA3. The smallest completely isolated segments of the CA3 field which spontaneously generated synchronized afterdischarges, comparable to those observed in the intact slice, measured 500-700 microns along the stratum pyramidable. It is concluded that these afterdischarges depend on local neuronal interactions mediated by chemical synaptic mechanisms which may occur within a single population of as few as 1000 CA3 pyramidal cells. The results are consistent with a repeated activation of the same group of synapses, which may release an excitatory amino acid neurotransmitter, being responsible for the initiation of each afterdischarge.