We have recently described an innovative drug delivery system, a water-based and vapor permeable film intended for dermal and/or transdermal delivery. The aim of this work was to modulate the delivery of the model drug lidocaine hydrochloride from the transdermal film across rabbit ear skin. The effect of drug loading, of film-forming polymer type and content, of adhesive and plasticizer on lidocaine transport across the skin was evaluated. Additional objective was to evaluate the effect of occlusion on the kinetics of lidocaine transport, by applying an occlusive backing on the surface of the transdermal film. From the data obtained it can be concluded that the transdermal film acts as a matrix controlling drug delivery. The film-forming polymer molecular weight had a negligible effect on drug penetration, while its content was more effective. The choice of the adhesive seems to be the most important variable governing drug transport. In particular, the presence of lauric acid combined with a basic drug, such as lidocaine, can produce a relevant improvement in permeation, because of the formation of an ion pair. Concerning the kinetics, drug depletion is responsible for the declining permeation rates observed in the late times of permeation.