Experiments in which several high and/or low frequency stimulation patterns were applied to different groups of afferents in CA1 hippocampal slices revealed the existence of heterosynaptic interactions between LTP and LTD. Specifically, we report that repeated induction of LTD on one input was associated with a heterosynaptic reversal of the LTP previously induced on a separate pathway. Reapplication of high frequency stimulation at the end of the experiment reinstated LTP. This heterosynaptic reversal occurred without modification of naive responses, and it was prevented by D-AP5, an NMDA receptor antagonist, or cyclosporin A, a calcineurin inhibitor. Similarly, induction of LTP on one input was found to reverse heterosynaptically the LTD previously induced on a separate pathway. This effect was also sensitive to D-AP5, it occurred without modification of naive pathways, and LTD could be reinstated by low frequency trains. These results indicate that repeated induction of LTP or LTD on one group of afferents can reset synaptic efficacy at other nonactivated synapses.