An in vitro study was carried out to elucidate the mechanisms controlling iontophoretic transport. The investigation focused on three areas, including the nature of the permeant (state of ionization and hydrophobicity), skin structures (hair follicle distribution and stratum corneum), and various parameters influencing iontophoresis (current, permeant concentration, and competitive ion effects). The data indicate that iontophoretic-facilitated transport is essentially pore mediated and that the transport of ionized and nonionized molecules may be enhanced through the pore-type pathway. The data presented show that iontophoresis has a detrimental effect on the lipoidal transport pathway and that the transport of more hydrophobic nonionized molecules is decreased compared with passive diffusion. The iontophoretic enhancement values decreased linearly with increasing alkyl chain length of n-alkanols. The iontophoretic permeability coefficients of ionized n-alkanoic acids was shown to decrease with increasing permeant hydrophobicity.