The percutaneous absorption of Morphine and Morphine hydrochloride is optimized using binary solvent systems as vehicle of the drugs. Release kinectics through hairless mouse skin are performed in vitro: variations of the flux, of the lagtime and of the cumulative released quantities as a function of the vehicle composition point out a synergistic effect of the two solvents (Labrafac hydrophile and Transcutol). Independant determinations of the skin/vehicle partition coefficient, of the solubility and of the diffusion coefficient are realized; the results allow us to explain the different enhancing effects of each solvent: the first one has an enhancing effect on the drug concentration in the skin, and the second one modifies the mobility of the drug in the skinThe rate of the drug release is usually optimized increasing the drug activity in the donor in relation with the solubility variation. With transdermal system (matrix, film) a more accurate approach is to increase the skin permeation of the drug (1) (2). This effect is commonly attempted with enhancers contained in the system, but a particular vehicle can act as an enhancer and as a solvent (3–7). In this case, we optimize the permeation coefficient, P = (K D/e), where K is the skin/vehicle partition coefficient, D is the diffusion coefficient and e is the skin thickness. The partition coefficient allows variation of the drug concentration in the skin, while the diffusion coefficient represents the mobility of the drug in the skinThe aim of this presentation is to analyze, on experimental data, the variation of the permeation to identifie, to localize, and to explain the role of a such vehicle. We studied the morphine permeation through hairless mouse skin with a binary solvents system. The solvents used are a diethylene glycol monoether (T) and a glycolysed ethoxylated glyceride (L). We propose to analyze the influence of the mixture composition on the partition and diffusion coefficient of morphine. We used an hydrophilic specie, morphine hydrochloride (MHCl), and a lipophilic specie, basic morphine (M), assuming that their routes of penetration are different: etheir hydrophilic inter or intra cellular route, or lipidic intercellular route. We suppose that each solvent can modifie the physical or chemical structure of these routes and consequently, the permeation of one particular specie of morphine