Ionic materials in solution do not penetrate the skin following local (topical) application. Such a low permeability can, however, be altered by iontophoresis. Utilization of transmission and scanning electron microscopy and cryostat techniques has made it possible to demonstrate the penetration and site of deposition of ionic tracers in the skin of the rat. It has been found that the penetration of cationic dyes and metal cations is facilitated by positive iontophoresis while the penetration of anionic dyes is facilitated by negative iontophoresis. The extent of penetration is determined by the current density, the concentration of the tracer in the vehicle, the physico-chemical properties of the tracers and the type of vehicle used. The removal of surface lipid is regarded as insignificant in terms of enhancing the penetration of tracers by iontophoresis. It has been found that the penetration of ionic tracers into the skin is preferentially transfollicular. However, the penetration of electron-dense tracers into the stratum corneum of the epidermis and the follicular infundibula is preferentially intercellular, while that into the sebaceous glands is transcellular. It is considered that the whole of the stratum corneum of the epidermis is the major barrier to cutaneous penetration by electrolytes. In addition, a barrier function is suggested for sebum situated in the follicular infundibula.