Stratum corneum, the outermost layer of the skin, offers a strong barrier to the movement of solutes as well as ions. We report on the existence of a relationship between skin's electrical impedance and its permeability to hydrophilic (mannitol and inulin) as well as hydrophobic (corticosterone and estradiol) solutes in the presence of 33 distinct chemical penetration enhancer formulations. The correlation between impedance and permeability was excellent (r2=0.8) for hydrophilic solutes and moderate, yet significant (r2 approximately 0.5), for hydrophobic solutes. The possibility of using skin's electrical impedance to choose potent formulations was quantitatively assessed. Percentile ranking of penetration enhancers based on their effect on skin's electrical impedance matched well with the ranking based on their effect on solute permeability (r2>0.9 for both mannitol and estradiol). These studies demonstrate the feasibility of using skin's electrical impedance to screen potent chemical enhancers.