The key to promoting percutaneous penetration is to alter the properties of the dermal barrier function. Mechanisms for changing the barrier function vary. Thus, some enhancers induce reversible conformational changes, whereas others cause prolonged barrier disruption. Discrimination between the influences of detergents on the barrier function may enable the use of those detergents affecting the overall integrity of the skin the least. In an experimental setup using in-vitro static diffusion cells mounted with human skin, the effects of four extensively used detergents on dermal barrier function were evaluated. Three of the detergents (lutensol AP10, nonyl phenyl ethoxylate, ethanol) apparently enhance percutaneous penetration without compromising the overall integrity of the skin barrier. SLS, on the other hand, acts through a time-and-dose-dependent deterioration of the dermal barrier function. The present experimental approach allows discrimination between detergents that act through different mechanisms to enhance percutaneous penetration.