The potential use of iontophoresis to improve drug penetration into the nail has been suggested. However. there is little information concerning transungual iontophoresis in vivo. This work describes the application of transungual iontophoresis to six healthy human volunteers in order to investigate key issues such as the effect of current application on ionic transport and on transonychial water loss (TOWL), and the magnitude of the voltages required for a practical use of the technique. Each volunteer participated in three experiments: passive control, 0.2 mA anodal transungual iontophoresis and 0.2 mA cathodal transungual iontophoresis. A commercial electrode on a skin site was used to complete the electrical circuit. The outward transungual extraction of sodium and chloride ions by passive diffusion and iontophoresis was quantified. Iontophoresis enhanced chloride and sodium transport similar to 8 and 27 fold respectively compared to passive diffusion. Sodium transport numbers were measured to be t(Na+) = 0.51 +/- 0.11. TOWL was used as a potential marker of nail damage and hydration. Basal TOWL was measured before each experiment, and the return to baseline values was monitored for I h after the treatment (passive or iontophoresis application) was finished. TOWL was increased after both iontophoretic and passive experiments and typically returned to baseline values in I h post-treatment. The voltage of the nail-to-skin circuit was monitored during iontophoresis and compared to those observed in a skin-to-skin circuit. Nail-to-skin circuit voltages were generally similar to 50 V when the current was started and dropped fast to 20-30 V, a value comparable to that observed in the skin-to-skin circuit. On the whole, the clear enhancement of ionic transport observed, the feedback from volunteers, the small effects in TOWL, and the magnitude of voltages indicate that nail DC current iontophoresis is feasible and probably a safe technique.