In the present work, we attempted to design a transdermal system for delivering selegiline using a hydrogel-based drug reservoir and a rate-controlling membrane (Solupor polyethylene membranes). The appearances of these preparations were evaluated by scanning electron microscopy (SEM), and the in vitro skin permeation of selegiline across porcine skin was examined. Both the R- and S-forms of selegiline were examined in this study to elucidate the stereoselectivity of skin to selegiline. Solupor membranes and hydrogels exhibited a cross-linking structure with micropores. R-Selegiline revealed a flux of 1.13 microg/cm(2)/h across porcine skin. Solupor membranes were rate limiting for skin permeation of selegiline. Around a 2-fold reduction in the drug flux was determined after Solupor membrane incorporation. There were no significant differences in drug flux across the four Solupor membranes tested. The flux of R-selegiline from cellulose hydrogels approximated that from the aqueous solution (control). Both the membrane and hydrogel greatly reduced the inter-subject variations in skin permeation. According to the results of skin permeation and the partition coefficient between the skin and water (logP(skin/water)), the S-enantiomer may be preferable for permeation into the skin. However, the R- and S-forms demonstrated equal absorption of the drug fluxed in the presence of the membrane and/or the hydrogel. The results of this study encouraged us to further investigate hydrogel-membrane delivery systems for transdermal selegiline administration.