It has been shown that signi®cant pore induction (electroporation) occurs in human epidermal membrane (HEM) during iontophoresis even at moderate applied voltages (1±10 V). Recent efforts in our laboratory have been aimed at quantifying HEM electroporation by examining the proportionality between ¯ux enhancement due to electroporation and electrical conductance changes during iontophoresis. The speci®c purpose of the present study was to test the hypothesis that by matching the background electrolyte ion sizes with the permeant ion sizes, the ¯ux enhancement due to electroporation can be quanti®ed by the change in HEM electrical conductance. In this study, radiolabeled tetraethylammonium (TEA ), methylammonium (MA ), and mannitol were the permeants. Potassium chloride (KCl), tetraethylammonium bromide (TEAB), tetraethylammonium pivalate (TEAP), and sodium ¯uoride (NaF) were the background electrolytes. Iontophoresis experiments were carried out over an applied voltage range of 1 to 3 V. The experimental ¯ux enhancement results were compared with the theoretical predictions from the Nernst±Planck model after corrections were made: (a) for HEM pore induction during iontophoresis based on electrical conductance changes and (b) for electroosmosis employing mannitol as the neutral probe permeant. In experiments where the ion sizes of the background electrolyte and permeant were closely matched (e.g., TEA as the permeant and TEAP as the background electrolyte), there was excellent agreement between experimental results and theoretical predictions of the modi®ed Nernst±Planck model, with only modest data scatter. When the electrolyte and permeant sizes were quite different (e.g., TEA /KCl and MA /TEAP), the experimental ¯ux data were inconsistent with model predictions and there were large variations in the experimental results. The results of the present study illustrate that permeant ¯ux enhancement can be predicted by the modi®ed Nernst-Planck model even during moderate voltage iontophoresis when electroporation is operative. ß