Pores through which charged carriers move during iontophoresis were demonstrated by the use of the cathodic (-) iontophoretic transport of fluorescein from the epidermis to the dermis. Both dermatomed (0.8-mm) human cadaver skin and full-thickness female human breast skin were investigated. The density of pores, as visualized by fluorescein transport, was approximately 2-5 cm-2. A set of microelectrodes rastered across the visualized pore gave a maximal response when directly above the pore, demonstrating that the pore was a locus of charge transport. Fluorescein was also sometimes observed at the diffusion cell-tissue interface. This indicates that edge damage had occurred as the result of clamping the tissue in a diffusion cell. Studies were conducted to determine if tissue damage occurred during iontophoretic transport. The electrical resistance across excised skin was measured at 0.2 Hz and found to decrease initially by approximately an order of magnitude after the application of an iontophoretic current of 0.16 mA/cm2 for 1 h. The electrical resistance then increased, reaching a plateau value which was lower than the original tissue resistance before application of an iontophoretic current. Controls were carried out to demonstrate that the observed electrical resistance changes were not just due to tissue hydration effects. These results imply that the passage of current through excised human skin at clinically acceptable current densities can lead to tissue damage which is not fully reversible.