Interstitial cells of Cajal (ICC) generate the electrical slow wave required for normal gastrointestinal motility. The ionic conductances expressed in human intestinal ICC are unknown. The aim of this study was to determine expression of a Na⁺ current in human intestinal ICC and to determine the effects of the Na⁺ current on the slow wave. Visually identified, freshly dissociated, single ICC were verified by the presence of c-kit mRNA by using single-cell RT-PCR. Standard whole cell currents were recorded from patch-clamped ICC held at -100 mV between pulse protocols. A Na⁺ current was identified in human intestinal ICC. The current activated at -55 mV and peaked at -30 mV. Extracellular N-methyl-d-glucamine abolished and QX-314 (500 μM) blocked the Na⁺ current, but nifedipine and Ni²⁺ did not. The Na⁺ current was activated by shear stress. Single-cell RT-PCR detected mRNA for the Na⁺ α-subunit SCN5A in single human intestinal ICC. Lidocaine (200 μm) and QX-314 (500 μM) decreased slow wave frequency, and stretch increased slow wave frequency. A mechanosensitive Na⁺ channel current is present in human intestinal ICC and appears to play a role in the control of intestinal motor function.