In standard protocols, the frequency of synaptic stimulation determines whether CA1 hippocampal synapses undergo long-term potentiation or depression. Here we show that during cholinergically induced theta oscillation (e) synaptic plasticity is greatly sensitized and can be induced by a single burst (4 pulses, 100 Hz). A burst given at the peak of e induces homosynaptic LTP; the same burst at a trough induces homosynaptic LTD of previously potentiated synapses. Heterosynaptic LTD is produced at inactive synapses when others undergo LTP. The synaptic modifications during e re quire NMDA receptors and muscarinic receptors. The enhancement is cooperative and occludes with standard LTP. These results suggest that the similar bursts observed during 0 rhythm in vivo may be a natural stimulus for inducing LTP/LTD.