The main objective of our study was to investigate skin function and structure in human volunteers after electrical current application in order to demonstrate the safety of iontophoresis in vivo. The direct current was applied for 30 min at a density of 0.1 and 0.2 mA/cm2. Iontophoresis increased cutaneous blood flow as measured by laser Doppler flowmetry (LDF). This increase was reversible within 1 h and was more pronounced at higher current density. Measurements of transepidermal water loss (TEWL) and LDF were the same at the cathode and the anode sites. Except for 5 min at 0.2 mA/cm2 density, TEWL values were not enhanced as compared to control values (no iontophoresis). Attenuated total reflectance-Fourier transform infrared spectroscopy of the stratum corneum structure showed a transient increase (30 min) in hydration after electrode application for 30 min. No alteration in lipid structure could be shown. These results augur the safety of drug delivery by iontophoresis.