In a previous study iontophoresis of glutamate on the apical dendrite of layer 5 pyramidal neurons from rat neocortex was used to identify sites at which dendritic depolarization evoked small, prolonged Ca2+ spikes and/or low-threshold Na+ spikes recorded by an intracellular microelectrode in the soma. These spikes were identified as originating in the dendrite. Here we evoke similar dendritic responses by electrical stimulation of presynaptic elements near the tip of the iontophoretic electrode with the use of a second extracellular electrode. In 9 of 12 recorded cells, electrically evoked excitatory postsynaptic potentials (EPSPs) above a minimum size triggered all-or-none postsynaptic responses similar to those evoked by dendritic glutamate iontophoresis at the same site. Both the synaptically evoked and the iontophoretically evoked depolarizations were abolished reversibly by blockade of glutamate receptors. In all recorded cells, the combination of iontophoresis and an EPSP, each of which was subthreshold for the dendritic spike when given alone, evoked a dendritic spike similar to that evoked by a sufficiently large iontophoresis. In one cell tested, dendritic spikes could be evoked by the summation of two independent subthreshold EPSPs evoked by stimulation at two different locations. We conclude that the dendritic spikes are not unique to the use of glutamate iontophoresis because similar spikes can be evoked by EPSPs. We discuss the implications of these results for synaptic integration and for the interpretation of recorded synaptic potentials.