The effects of some essential vehicles in cosmetics or topical preparations for transepidermal water loss (TWL) and skin surface lipids were investigated on human skin in relation to their physicochemical properties. The test vehicles were isopropyl myristate (IPM), liquid paraffin 70cs (LPC70) and glycerol. The results revealed newer biopharmaceutical aspects concerning the mode of vehicles against skin surface as follows. 1) The degree of occlusive effect for TWL in the closed experimental system was graded in the following order : glycerol>LPC70>IPM. 2) The removal effect for sebaceous squalene and epidermal cholesterol was found to be in the following order : IPM>LPC70>glycerol. 3) The occlusive effect of vehicles on TWL was suggested to be inversely related to the removal effect of vehicles for skin surface lipids. 4) Vehicle viscosity seemed to be one of the physicochemical regulating factors for occlusive nature of vehicles against TWL. 5) The in vitro water loss test seemed to be meaningful for a better understanding of the vehicle effect on TWL. 6) The importance of the removal effect on epidermal cholesterol that reflected TWL increase was suggested in the evaluation of vehicles against human skin surface barrier properties.