The effects of 13-cis-retinoic acid and ginseng saponin iron Korean red ginseng on hyperkeratinization of guinea pig skin were investigated by means of enzymatic analysis and light microscopic observation. To induce hyperkeratinization, hexadevance It was topically applied to the dorsal skin of female guinea Pigs every other day for eight days and 13-cis- retinoic acid or ginseng saponin solution was administered orally or topically applied daily during the experimental period. As a result, both topical application of ginseng saponin and oral administration of 13-cis-retinoic acid showed prepentive effects on hyperkeratinization while topical application of 13-cis-retinoic acid inhibited normal epidermal cell proliferation and reduced epidermal enzyme activities such as LDH. ICD and GSPDH below the levels in a normal epidermis. It is suggested that topical application of ginseng saponin and oral administration of 13-cis-retinoic acid may have beneficial efforts against hyperkeratinization possibly by controlling epidermal proliferation and enzyme activities related to epidermal energy metabolism.