The effects of oleic acid, propylene glycol and 5% (w/w) oleic acid in propylene glycol on the electrical properties of hairless mouse skin were studied and the results were compared. The complex electrical impedance was measured as a function of frequency, and resistance and capacitance were determined from the Nyquist plot. Immediately after the treatment with oleic acid, resistance was 145% of the pretreatment value. However it decreased with time and, after 20 hours, it was about 25% of its pretreatment value. Capacitance increased; immediately after the treatment, it was about 125% of pretreatment value and it seemed to increase slowly with time. When the skin was treated with propylene glycol, resistance decreased about 5O% and capacitance increased about 65%. Similar results were observed when the skin was treated with 5% (w/w) oleic acid in propylene glycol, except that the magnitude of resistance drop was much larger. Oleic acid acted synergistically with propylene glycol. Together with the flux data in the literature, the results obtained in this work indicate that electrical resistance is closely related to the permeability of drug molecules through the skin. The results are discussed in terms of the mechanism of action of these penetration enhancers. Overall, this work provided further mechanistic insight into the role of SC lipids in skin resistance and capacitance.