Sharp waves (SPWs) occur in the hippocampal EEG during behaviors such as alert immobility and slow-wave sleep. Despite their widespread occurrence across brain regions and mammalian species, the functional importance of SPWs remains unknown. Experiments in the present study indicate that long-term potentiation (LTP) is significantly impaired in slices, prepared from the temporal aspect of rat hippocampus, that spontaneously generate SPW activity. This was likely not due to anatomical and/or biochemical abnormalities in temporal slices because stable LTP was uncovered in field CA1 when SPWs were eliminated by severing the projection from CA3. The same procedure did not alter LTP in slices lacking SPWs. Robust and stable LTP was obtained in the presence of SPWs in slices treated with an adenosine A1 receptor antagonist, a finding that links the present results to mechanisms related to the LTP reversal effect. In accord with this, single stimulation pulses delivered intermittently in a manner similar to the SPW pattern interfered with LTP to a similar degree as spontaneous SPWs. Taken together, these results suggest the possibility that SPWs in the hippocampus constitute a neural mechanism for forgetting.