We observed in this study that transient periodic stimuli in response to high potassium (40 mM, 5 min at 40-min intervals, 13-15 stimuli) perfusion in the ventral hippocampus of rats led to the appearance of a kindling-like phenomenon. In this kindling-like phenomenon, we confirmed the augmentation of glutamate release and the prolongation of spike discharge. Changes in the extracellular glutamate levels before and after the stimuli were monitored by the application of in vivo microdialysis combined with on-line enzyme fluorometric detection of glutamate. This kindling-like phenomenon was not observed when microdialysis was carried out using a Ca++-free medium. The augmentation of glutamate release and the prolongation of spike discharge with epileptic convulsions are completely Ca++ dependent. These data show that repeated short-term increases in extracellular glutamate levels results in the enhancement of excitatory neuronal systems, causing an excessive propagation of seizure activity and culminating in secondary generalized seizures.