Recent reports indicate that the exposure of brain tissues to transcranial magnetic stimulation induces persistent changes in neuronal activity and influences hippocampal synaptic plasticity. However, the modulation of synaptic efficiency by magnetic stimulation in vitro is still unclear. In the present study, we investigated whether high-frequency magnetic stimulation (HFMS) can induce long-term potentiation (LTP) in rat hippocampal slices in vitro. During baseline recording and after HFMS, field excitatory postsynaptic potentials (fEPSPs) were recorded within the CA1 stratum radiatum in response to electrical stimulation of the Schaffer collateral inputs. For LTP induction, HFMS was delivered through a circular coil positioned closely above the slices using two different paradigms (A: 10 trains of 20 pulses at 100 Hz with 1s intervals, 5 repetitions with 10s intervals; B: 3 trains of 100 pulses at 100 Hz with 20s intervals). The intensity of the magnetic stimulus was adjusted to 60-75 A/micros. After application of HFMS, electrically evoked CA1 fEPSPs were enhanced showing significant levels of LTP by both paradigms (A: 142+/-9% of baseline, n=6; B: 129+/-7%, n=8). Furthermore, HFMS-induced LTP induced by paradigm A was prevented by the presence of the selective N-methyl-D-aspartate receptor (NMDAR) blocker D-AP5 (50 microM) in the bath solution (95+/-6% of the baseline, n=6; p<0.01 compared to control condition without D-AP5). Further, the lack of changes in paired-pulse ratio and the afferent fiber volleys exclude presynaptic involvement in HFMS-induced LTP. In summary, we have demonstrated that HFMS can induce NMDAR-dependent LTP in the CA1 region in vitro.