The effects of applied voltage and the duration of application upon human epidermal membrane (HEM) alterations and recovery were investigated. All experiments were conducted using a two-chamber diffusion cell with constant DC voltage (250-4000 mV) applied over a predetermined period, and HEM changes were monitored by measuring the electrical resistance before and after voltage termination. The key findings were that the rate of decrease in resistance was strongly dependent upon the applied voltage, the reversible recovery times were dependent upon both the magnitude and the duration of the applied field (frequently were several orders of magnitude greater than times for attaining significant resistance reduction), and reversible recovery times were much longer when lower voltages were applied for longer times to attain the same decrease in electrical resistance than for higher voltages at short times. These findings closely parallel those obtained on electrical breakdown/recovery of bilayer membranes (electroporation). The second part of this work examined the hypothesis that decreases in HEM electrical resistance induced by the applied voltage are accompanied by proportional increases in HEM permeability. A study was designed to test this hypothesis involving a four-stage protocol with HEM: passive transport, 250-mV iontophoresis, 2000-mV iontophoresis for 10 min, then back to 250-mV iontophoresis. The data obtained strongly support the view that the HEM alterations induced by the electric field result in pore formation and in the expected changes in HEM permeability.