The hippocampus plays a central role in memory formation in the mammalian brain. Its ability to encode information is thought to depend on the plasticity of synaptic connections between neurons. Pyramidal neurons from the CA3 produce monosynaptic excitatory postsynaptic potentials (EPSPs) followed rapidly by feedforward (disynaptic) inhibitory postsynaptic potentials (IPSPs). Long-term potentiation (LTP) of glutamatergic EPSPs is the leading model of synaptic plasticity, in part due to its dependence on NMDA receptors (NMDARs), which are also required for spatial and temporal learning in intact animals. Using whole-cell recording in hippocampal slices from adult rats, we find that the efficacy of synaptic transmission from CA3 to CA1 can be enhanced without the induction of glutamatergic LTP. We show that the induction of GABAergic plasticity at feedforward inhibitory inputs results in the reduced shunting of excitatory currents, producing a long-term increase in the amplitude of Schaffer collateral-mediated postsynaptic potentials. This GABAergic plasticity weakens inhibition due to a depolarization of the reversal potential for GABAA receptor currents (EGABA) through a decrease in the function of the neuron-specific K+-Cl- cotransporter KCC2. This form of inhibitory synaptic plasticity is termed disinhibition-mediated long-term potentiation (LTP). We found that disinhibition-mediated LTP is not restricted to the paired pathway, but rather is expressed to the same extent at unpaired control pathways. However, the overall strength of GABAergic transmission is maintained at the unpaired pathway by a heterosynaptic increase in GABAergic conductance. The pairing-induced depolarization of EGABA at the paired and unpaired pathways required Ca2+-influx through both the L-type voltage-gated Ca2+ channels and NMDA receptors. However, only Ca2+-influx through L-type channels was required for the increased conductance at the unpaired pathway. As a result of this increased GABAergic conductance, disinhibition-mediated LTP remains confined to the paired pathway and thus is synapse specific, suggesting it may be a novel mechanism for hippocampal-dependent learning and memory.