Neurons are flexible electrophysiological entities in which the distribution and properties of ionic channels control their behaviors. Through simultaneous somatic and axonal whole-cell recording of layer 5 pyramidal cells, we demonstrate a remarkable differential expression of slowly inactivating K(+) currents. Depolarizing the axon, but not the soma, rapidly activated a low-threshold, slowly inactivating, outward current that was potently blocked by low doses of 4-aminopyridine, alpha-dendrotoxin, and rTityustoxin-K alpha. Block of this slowly inactivating current caused a large increase in spike duration in the axon but only a small increase in the soma and could result in distal axons generating repetitive discharge in response to local current injection. Importantly, this current was also responsible for slow changes in the axonal spike duration that are observed after somatic membrane potential change. These data indicate that low-threshold, slowly inactivating K(+) currents, containing Kv1.2 alpha subunits, play a key role in the flexible properties of intracortical axons and may contribute significantly to intracortical processing.