A mechanosensitive Na+ current carried by Nav1.5 is present in human intestinal circular smooth muscle and contributes to regulation of intestinal motor function. Expression of this channel in different species is unknown. Our aim was to determine if Na+ currents and message for the α subunit of the Na+ channel (SCN5A) are found in circular smooth muscle cells of human, dog, pig, mouse and guinea pig jejunum. Currents were recorded using patch clamp techniques. Message for SCN5A was investigated using laser capture microdissection and reverse transcription polymerase chain reaction (RT-PCR). Na+ currents were identified consistently in human and dog smooth muscle cells; however, Na+ current was not found in pig (0/20) or guinea pig smooth muscle cells (0/21) and found only one mouse cell (1/21). SCN5A mRNA was found in circular muscle of human, dog, and mouse, but not in pig or guinea pig, and not in mouse longitudinal or mucosal layers. In summary, SCN5A message is expressed in, and Na+ current recorded from, circular muscle layer of human and dog but not from pig and guinea pig. These data show that there are species differences in expression of the SCN5A-encoded Nav1.5 channel, suggesting species-specific differences in the electrophysiological response to mechanical and depolarizing stimuli.