In the hippocampus, fast excitatory synaptic transmission of principal projection neurons is mediated by non-NMDA glutamate receptors, whereas NMDA glutamate receptors serve a slower modulatory role. We used the whole-cell patch-clamp technique in adult hippocampal slices to assess the role of NMDA receptors in synaptic excitation of a recently discovered excitatory projection neuron, the CA1 radiatum giant cell (RGC). Glutamatergic synaptic activation, even after blocking non-NMDA receptors, fired an NMDA receptor-dependent burst of action potentials in RGCs. In contrast, the contribution of NMDA receptors to synaptic activation of pyramidal cells (PCs) was minimal. Stimulation of the same synaptic inputs evoked greater than threefold larger EPSCs in RGCs than in PCs. Isolated NMDA receptor-mediated EPSCs were significantly less sensitive to blockade by extracellular Mg(2+) and had slower decay kinetics in RGCs than in PCs. Thus, unique properties of synaptic NMDA receptors underlie enhanced synaptic excitability in a newly discovered excitatory hippocampal projection neuron.