The effect of pulsed electromagnetic fields on the electrical potential and two-way flux of Na+ across the epithelium of the rabbit colon in vitro was investigated. In control experiments the transepithelial mucosal-to-serosal and serosal-to-mucosal fluxes (Jm----s and Js----m) were constant over the experimental period. When the epithelium was at right angles to the applied electromagnetic field, the Jm----s flux of Na+ was reduced, whereas Js----m was enhanced. When the epithelium was rotated 180 degrees, Jm----s was enhanced, whereas Js----m was reduced. When the epithelium was mounted parallel to the magnetic field, both Jm----s and Js----m of Na+ were increased, the latter continuing to increase after the field was turned off. When the tissue was rotated 180 degrees, the same enhanced flux was observed, but now the Jm----s flux showed the greatest increase, which again occurred in the period after the field was turned off. The rate of decrease of transepithelial potential difference in all orientations was less than the control. Also, the conductance increased in orientations 2-4 and decreased in orientation 1 after the field had been applied. This suggests that pulsed electromagnetic fields can have a direct effect on the movement of Na+ across tissue and transepithelial potentials. The mechanism may depend on several factors, such as induced changes in certain ion pumps, the membrane potential, and the surface charge of cell wall proteins.