Human autopsy skin was sliced into three sections; an outer epidermis-rich layer, a middle dermis layer, and an inner dermis and subcutaneous fat layer. Each slice was bathed in lindane solutions over a 50-fold concentration range for 48 h at 37°C. Lindane uptake by the skin was extensive (< 90%) for all concentrations and all skin slices. Equilibrium dialysis with lindane at 37°C for 24 h showed binding affinities by the skin sections to exceed 98%. The binding constants of the outer skin section (epidermis-rich) were higher than those of the middle and inner sections. The binding attraction for lindane by United States Pharmacopeia (USP) human plasma protein fraction (mean 90.5% bound) resulted in its competitive extraction from the skin slices in a three-compartment dialytic procedure. Since the least binding constants were in the middle and inner layers, and since lindane has a preference for plasma over skin, the two (inner skin and plasma) may combine to create the sink conditions necessary for lindane percutaneous absorption into the body. This plus the high epidermis capacity for lindane explains why in some instances (such as occlusion) high levels of lindane can be percutaneously absorbed.