It is a general rule that percutaneous absorption is increased when the site of application is occluded. In this study we compared the in vitro permeation profiles of two molecules with different physicochemical properties under occluded versus unoccluded conditions. Human abdominal skin samples were mounted on Dianorm® Teflon® macro 1 cells and Franz diffusion cells which represented occluded or unoccluded conditions, respectively. Our data show that occlusion increased the permeation of citropten (lipophilic compound) 1.6 times whereas that of caffeine (amphiphilic compound) remained unchanged. This lack of penetration enhancement under occluded conditions has also been observed by other authors, especially concerning hydrophilic and slightly lipophilic molecules. Our results support the view that occlusion does not necessarily increase the percutaneous absorption of a chemica