Activity-dependent changes in synaptic strength are important for learning and memory. Long-term potentiation (LTP) of glutamatergic excitatory synapses following brief repetitive stimulation provides a compelling cellular model for such plasticity. In the CA1 region of the hippocampus, anatomical studies have revealed large numbers of NMDA (N-methyl-D-aspartate) receptor sites at excitatory synapses, which express primarily an NMDA receptor-dependent form of LTP. In contrast, these studies have suggested that mossy fibre synapses activate primarily or exclusively alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and, indeed, these synapses express a form of LTP that is entirely independent of NMDA receptors. Here we present physiological data demonstrating that mossy fibres activate a substantial NMDA receptor synaptic component that expresses LTP. The presence of an NMDA receptor response allowed us to use the open-channel NMDA receptor antagonist MK-801 to establish directly that the probability of transmitter release is enhanced during the expression of mossy fibre LTP.