The influence of temperature on the resistive and capacitative properties of human stratum corneum in vitro was studied to determine where within substructures of stratum corneum, the electrical resistance R and capacitance C components reside. Heating-cooling cycles were designed in accordance with earlier calorimetric and spectroscopic studies of thermal transitions of human stratum corneum lipids and/or proteins. Two different protocols were used. (A) Heat treatment and electrical analysis were carried out simultaneously in pH 7.4 phosphate buffered saline, starting with prehydrated stratum corneum (70% w/w) of pH 7.4. (B) Heat treatment was performed before electrical analysis, using dried stratum corneum (< 10% w/w), followed by prehydration and measurement of the electrical properties in phosphate buffered saline at 20-degrees-C. Square-wave alternating current pulses of 13 muA cm-2 were applied every 60 s. Analysis of the resulting voltage waveform across stratum corneum yielded an equivalent electrical model of stratum corneum composed of a series connection of two RC circuits (R1 parallel-to C1 and R2 parallel-to C2). Below 60-degrees-C a constant activation energy of 5.4 +/- 0.7 kcal mol-1 was measured, which was close to the activation energy of K+ diffusion in a fluid aqueous medium. The total resistance of stratum corneum was less than 100 kOMEGA cm2, which is very low compared to the resistance of black lipid membranes (1-10 MOMEGA cm2). Both the low activation energy and resistance of human stratum corneum suggest the presence of highly conductive pathways through the membrane. Between 60 and 75-degrees-C an abrupt decline of the resistances R1 and R2 and a rapid rise of the capacitances C1 and C2 was observed. This temperature interval corresponded to the temperature interval of the second thermal transition observed in human stratum corneum, which is a lipid phase transition. Beyond 75-degrees-C, the resistances were fairly constant, while the capacitances continued to increase. The changes in the resistances and capacitances brought about by heating to 75 and 95-degrees-C were completely irreversible. This is in agreement with X-ray diffraction studies, which