The neurophysiological properties of human dentate granule cells were studied in hippocampal slices prepared from patients undergoing surgical treatment for medically intractable temporal lobe epilepsy. In 24 neurons which were morphologically identified as dentate granule cells by intracellular staining with biocytin, there were 2 types of synaptic responses to perforant path stimulation: one showed an EPSP-IPSP sequence (n = 10) and the other showed prolonged EPSPs without accompanying hyperpolarizing IPSPs (n = 14). The prolonged EPSPs were markedly retarded by the application of an NMDA receptor antagonist, APV. Membrane properties of neurons showing the different classes of synaptic responses were similar in resting membrane potential (pooled average: -56.2 mV +/- 0.94 SEM) and spike amplitude (pooled average: 65.2 mV +/- 1.69 SEM). However, membrane resistance tended to be lower in neurons with prolonged EPSPs (31.8 M omega +/- 2.63 SEM) than in neurons that showed EPSP-IPSP responses (40.2 +/- 4.33) (P less than 0.05, Fisher). No spontaneous and/or evoked burst firing was observed. These data provide fuller information on the neurophysiological properties of human dentate granule cells in surgically resected epileptogenic hippocampus, implicating a role of NMDA receptor activation in human temporal lobe epilepsy.