We studied with the whole-cell recording techniques, the mechanisms underlying the time course of the slow N-methyl-D-aspartate (NMDA), and fast non-NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) in hippocampal slices. The rising phase of the NMDA receptor-mediated component of the EPSC as well as the decaying phase of the NMDA and non-NMDA component were highly temperature-sensitive, suggesting that neither of these processes is determined by free diffusion of transmitter. Moreover, glutamate uptake blockers enhanced the responses to exogenously applied glutamate, but had no effect on the decay of either the NMDA or non-NMDA components of the EPSCs. On the other hand, open channel blockers known to modify NMDA channel kinetics reduced the EPSC decay time. Thus, the present results support a model in which the rise time and decay of the NMDA component are determined primarily by slow channel kinetics and the decay of the non-NMDA component is due either to channel kinetics or to desensitization.