Preventive effect of red ginseng saponin on experimentally-induced hyperkeratosis was investigated by ultrastructural observation, skin weight and epidermal lipid analysis. Hexadecane increased skin weight per unit area and epidermal lipids, free fatty acids, cholesterol and triglyceride in guinea pig skin. Topical application of ginseng saponin reduced these hyperkeratotic responses regradless of the concentration and the purity of ginseng saponin. Ultrastructurally, lipids and empty space-containing multiple horny cells were piled and nuclear remnants, desmosome, desmosomal bodies, tight junction were shown in the stratum corneum of hexadecane-treated skin,