Voltage-activated Na+ channels in the primary sensory neurons are important for generation of action potentials and regulation of neurotransmitter release. The Na+ channels expressed in different types of dorsal root ganglion (DRG) neurons are not fully known. In this study, we determined the possible difference in tetrodotoxin-sensitive (TTX-S) and -resistant (TTX-R) Na+ channel currents between isolectin B4 (IB4)-positive and IB4-negative small DRG neurons. Whole-cell voltage- and current-clamp recordings were performed in acutely isolated DRG neurons labeled with and without IB4 conjugated to Alexa Fluor 594. The peak Na+ current density was significantly higher in IB4-negative than IB4-positive DRG neurons. While all the IB4-negative neurons had a prominent TTX-S Na+ current, the TTX-R Na+ current was present in most IB4-positive cells. Additionally, the evoked action potential had a higher activation threshold and a longer duration in IB4-positive than IB4-negative neurons. TTX had no effect on the evoked action potential in IB4-positive neurons, but it inhibited the action potential generation in about 50% IB4-negative neurons. This study provides complementary new information that there is a distinct difference in the expression level of TTX-S and TTX-R Na+ channels between IB4-negative than IB4-positive small-diameter DRG neurons. This difference in the density of TTX-R Na+ channels is responsible for the distinct membrane properties of these two types of nociceptive neurons.