We evaluated the characteristics of the persistent sodium current (I_NaP) in layer II/III and V pyramidal neurons in slices of rat sensorimotor cortex using whole-cell patch-clamp recordings. In both layers, I_NaP began activating around -60 mV and was half-activated at -43 mV. The I_NaP peak amplitude and density were significantly higher in layer V. The voltage-dependent I_NaP steady-state inactivation occurred at potentials that were significantly more positive in layer V (V_1/2 :-42.3 ±1.1 mV) than in layer II/III (V_1/2:-46.8±1.6 mV). In both layers, a current fraction corresponding to about 25% of the maximal peak amplitude did not inactivate. The time course of I_NaP inactivation and recovery from inactivation could be fitted with a bi-exponential function. In layer V pyramidal neurons, the faster time-constant of development of inactivation had variable values, ranging from 158.0 to 1133.8 ms, but it was on average significantly slower than in layer II/III (425.9±80.5 vs. 145.8 ±18.2 ms). In both layers, I_NaP did not completely inactivate even with very long conditioning depolarizations (40s at -10 mV). Recovery from inactivation was similar in the two layers. Layer V intrinsically bursting and regular spiking non-adapting neurons showed particularly prolonged depolarized plateau potentials when Ca²⁺ and K⁺ currents were blocked, and slower early phase of I_NaP development of inactivation. The bi-exponential kinetics characterizing the time-dependent inactivation of I_NaP in both layer II/III and V indicates a complex inactivating process that is incomplete, allowing a residual "persistent" current fraction that does not inactivate. Moreover, our data indicate that I_NaP has uneven inactivation properties in pyramidal neurons of different layers of rat sensorimotor cortex. The higher current density, the rightward shifted voltage dependence of inactivation as well the slower kinetics of inactivation characterizing I_NaP in layer V with respect to layer II/III pyramidal neurons may play a significant role in their ability to fire recurrent AP bursts, as well in the high susceptibility to generate epileptic events.