Nasal transepithelial electrical potential difference (PD) was estimated in vivo in normal human subjects. The PD between a bridge perfused with Ringer's solution placed on the nasal mucosal surface and a reference electrode in a subcutaneous space was recorded. The magnitude of the PD depended upon the region of the nasal cavity touched by the exploring bridge. The PD values ranged from -4 mV (lumen negative) on the anterior tip of the inferior turbinate to approximately -30 mV on the inferior surface of the turbinate. Biopsies of the anterior turbinate were characterized by squamous epithelial cells, whereas ciliated cells dominated the epithelium from regions of higher PD. Epithelial abrasion abolished PD. No differences in PD were noted between the left and right nasal cavities, and repetitive measurements of PD at the same site yielded comparable values. No differences in nasal PD were noted between young male or female subjects but PD declined as a function of age. Amiloride (10(-4)M) and lidocaine (10(-1)M) reduced PD (-59% and -30%, respectively), whereas amphotericin B (5 X 10(-5)M) raised PD (+29%). We concluded that nasal PD can be accurately measured in vivo in humans, and that measurements of nasal bioelectric properties may serve as a relatively noninvasive index of respiratory epithelial function.