The influence of ethanol on the transport behavior of β-estradiol and other permeants in hairless mouse skin was investigated over a 0–100% ethanol/saline concentration range. At high ethanol levels (> 50%), there were significant increases in new pore formation in the stratum corneum component of the skin. With pure ethanol, pore pathway transport dominated the permeation for all solutes, irrespective of polarity. At low ethanol levels (<25%), ethanol had little or no effect on the pore pathway. However, the transport of β-estradiol and hydrocortisone via the lipid pathway of the stratum corneum was greatly enhanced. The enhancement factor, E, for β-estradiol and for hydrocortison was calculated from the experimental permeation data by correcting for the dermis /epidermis permeability coefficient, the stratum corneum pore pathway permeability coefficient, and by using solubility data to correct for chemical potential changes with solvent composition. The E-values for β-estradiol and for hydrocortisone were found to be of the same magnitude (7 to 9 at 25% ethanol and of the order of 100 at 50% ethanol). It is proposed that the ethanol enhancement effects at low ethanol levels may be interpreted in terms of fluidity increases in the transport rate-limiting lipid domains.