We tested the hypothesis that action potentials originate in apical dendrites of pyramidal cells. Layer V somata were voltage clamped in thin slices of rat motor cortex. Fibers synapsing in unclamped regions far out on the apical dendrite caused small, slow synaptic currents, as recorded at the soma, and sometimes elicited complex, multicomponent current spikes, beginning with a small first spike. Hyperpolarization, or tetrodotoxin applied to basal dendrites and soma, blocked the later spike components without affecting the synaptic current and the first component, which was a synaptically triggered Na+ spike in the apical dendrite. Similar spikes followed voltage steps or direct stimulation. We conclude that Na+ action potentials are initiated in the apical dendrite in response to synaptic input.