There are two groups of mechanisms through which ultrasound can affect biological systems, those of thermal origin and others of nonthermal origin. Since in almost every therapeutic application of ultrasound, movement of ions across cellular membranes is involved, it becomes important to study the effect of ultrasound on active and passive ionic conductance. In order to differentiate between thermal and nonthermal effects, a study was conducted on model systems in which the effect of temperature is known. The well-known sodium transporting epithelium, the epidermis of abdominal frog skin, was investigated and the effect of therapeutic ultrasound on its electrophysiological properties was determined. It was found that under open circuit conditions, irradiation of the skin with 1 MHz cw (60-480 mW/cm2) ultrasound caused a significant decrease (5-50%, depending on the applied power) in the transepithelial potential and resistance at room temperature (20-22 degrees C). Under short circuit conditions, also at room temperature, there was an increase in total ionic conductance (20-250%, depending on the applied power) and a decrease in the net actively transported current, measured as the short circuit current. These effects are reversible within the range of powers used. Furthermore, it was found that the magnitude of the observed changes was strongly dependent on the perfusion rate and the gas content of the bathing medium. The effect of ultrasound diminished in the presence of CO2 and was enhanced with faster perfusion rates. Pulsed ultrasound delivered at the same energy (Isata) as that of cw caused a significantly larger effect. At lower temperatures (12-14 degrees C) the effect of ultrasound was reduced. Analysis of the data reveals that the effects of ultrasound on ion transport reported here are not primarily of thermal origin but are probably due to cavitation and related effects, such as microsteaming.