We previously reported the post-ischemic potentiation (PIP) of synaptic efficacy in hippocampal Schaffer collateral/CA1 responses of the rat beginning at 6-8 h following 12 min transient cerebral ischemia in vivo. The present study demonstrated that repetitive stimulation with a relatively low frequency (5 Hz, 6 s), which produced short-lasting afterdischarges (ADs; duration, 4.49 +/- 4.26 s; n = 7) in sham-controls, resulted in prolonged ADs (duration, 26.33 +/- 12.63 s; n = 6; P < 0.001) at the same period after ischemia. The PIP was not affected by 2-amino-5-phosphonovalerate (APV) administered via microdialysis at 7 h post-ischemia. The prolonged ADs in response to repetitive stimulation were, however, reversed to short-lasting ADs (duration, 7.13 +/- 1.44 s; n = 4; P < 0.02) by the same procedure, leaving the response to single stimulation unaffected. These findings suggest that, during the reperfusion period, Ca2+ influx into the CA1 pyramidal cells can be greatly increased through N-methyl-D-aspartate (NMDA) receptor-coupled ion channels if appropriately timed multiple synaptic inputs bombard these cells. Such Ca2+ influx may contribute to delayed death of CA1 pyramidal cells after transient cerebral ischemia if synaptic activity is maintained at relatively high levels during the reperfusion period.