In order to clarify the roles of lipids in the water-holding property of stratum corneum, the forearm skin of healthy male volunteers was treated with acetone/ether (1/1) or sodium dodecyl sulfate (5%) for 1-30 min.A prolonged treatment period of 5-30 min produced a chapped and scaly appearance of the stratum corneum without any inflammatory reactions.Under these conditions, there was a marked decrease in the water-holding capacity of the stratum corneum accompanied by a selective loss of stratum corneum lipids such as cholesterol, cholesterol esters, and sphingolipids. Two daily applications of the isolated stratum corneum lipids to experimentally induced dry skins caused a significant increase of conductance r accompanied by a marked improvement in the level of scaling.Meanwhile, the isolated sebaceous lipids exhibited no significant recovery in both the conductance value and the scaling.Out of chromatographically separated fractions of the stratum corneum lipids, topical applications of ceramide fraction induced the highest increase in the conductance value.Topical applications of synthesized pseudo-ceramides also showed a significant recovery of the water-retaining properties accompanied by an improvement in the scaling only when the polar group has an amide bond in the major linkage.Analysis of the alkyl chain structures has revealed that a structural requirement for the recovery of the water retaining capacity is the presence of saturated-straight alkyl chains, not unsaturated or branched alkyl chains. These structural characteristics required for water-retaining function also paralleled their capacity to form multiconcentric lamellae vesicles in vitro which is also capable of acquiring bound water as shown by """"DSe-t'Fiermograms. The present study suggests that ceramides with relatively shorter alkyl chain length serve as a water modulator in the multi-lipid bilayers through the stratum corneum.