A high density of Na+ channels in the axon hillock, or initial segment, is believed to determine the threshold for action potential initiation in neurons. Here we report evidence for an alternative mechanism that lowers the threshold in the axon. We investigated properties and distributions of ion channels in outside-out patches from axons and somata of layer 5 pyramidal neurons in rat neocortical slices. Na+ channels in axonal patches (<30 microm from the soma) were activated by 7 mV less depolarization than were somatic Na+ channels. A-type K+ channels, which were prominent in somatic and dendritic patches, were rarely seen in axonal patches. We incorporated these findings into numerical simulations which indicate that biophysical properties of axonal channels, rather than a high density of channels in the initial segment, are most likely to determine the lowest threshold for action potential initiation.