Most drugs permeate biological membranes via passive diffusion and it is generally assumed that the main barrier is the lipophilic structure of the membrane. However, we have observed that the unstirred water layer adjacent to the membrane surface can in some cases be a barrier just as effective as the lipophilic membrane itself. Hydrophilic cyclodextrins can enhance drug delivery through biological membranes by increasing the availability of dissolved drug molecules immediate to the membrane surface, i.e. by increasing drug delivery through the unstirred water layer. Cyclodextrins and drug/ cyclodextrin complexes are, in most cases, unable to permeate lipophilic membranes. Thus, excess cyclodextrin, more than is needed to solubilize the drug in the aqueous exterior, will hamper drug delivery through biological membranes.