The effect of urea on the horny layer of human epidermis has been studied with special regard to its osmotic and keratolytic effects. It has been shown that the water-binding capacity mainly must be of osmotic nature; the same effects could be achieved with about half the concentration (w/w) of sodium chloride. Pieces of upper epidermis kept in saturated urea solutions changed mechanically already after 1 week, and later it could be seen that the original quaternary structure of keratin is lost. No such changes could be seen in saturated sodium chloride solution. The results indicated that urea-containing creams, although certainly valuable in hyperkeratotic conditions, should be used with care as long-term cosmetical products.