Simultaneous somatic and dendritic recordings were made from the same neocortical layer V pyramidal neuron, and current injection via the dendritic recording pipette was used to simulate the voltage change that occurs during an EPSP. At the soma, these simulated EPSPs increased nonlinearly with the amplitude of the dendritic current injection and with depolarization of the membrane potential. Bath application of the sodium channel blocker TTX decreased large (> 5 mV) EPSPs and also blocked amplification of EPSPs at depolarized membrane potentials, whereas calcium channel blockers had little effect. Local application of TTX to the soma and axon blocked EPSP amplification, whereas dendritic application had little effect. Simultaneous somatic and axonal recordings demonstrated that EPSP amplification was largest in the axon. These results show that EPSPs are amplified by voltage-activated sodium channels located close to the soma and in the axon.