During the application of high-voltage pulses across the skin, transport of two negatively charged fluorescent molecules through the stratum corneum is highly localized. The apparent size of these localized transport regions (LTR's) is initially 10 microns in diameter for both calcein and sulforhodamine. Appearance of LTR's occurred at or above transdermal voltages of 75 V. In the range of 75 to 160 V, the number of LTR's increases with voltage, but their initial size is the same at all voltages; with additional pulses LTR's increase in size, reaching diameters of approximately 40-80 microns. Small ion currents across the skin are also localized and include the LTR's; however, the areas of current flux appeared to be larger. There was no visible damage to the structure of the skin seen at 100 x magnification for any of the voltages used (< 170 V across the skin). Significantly, LTR's are not sweat ducts or hair follicles.