The objective of the present study was to design and evaluate unilaminate transdermal adhesive matrix systems capable of diffusing bupropion base at a constant rate over an extended period of time as an alternative route of administration. Unilaminate transdermal adhesive matrices have been fabricated with different concentrations of Eudragit E as the adhesive and rate-controlling polymer. The in vitro release and epidermal flux through human cadaver skin were studied. The release of drug from the matrices obeyed zero order release kinetics (r2 = 0.9810 to 0.9960). The delivery rate of bupropion ranged from 10.5 mg to 31.4 mg per day from a 3.14 cm2 area of matrix. The relation between concentration of bupropion base in matrix and epidermal flux, concentration of drug in matrix, and epidermal adsorption of bupropion during diffusion follow hyperbolic fashion. Triethylcitrate (TEC) and dibutylphthalate (DBP) have no influence on the diffusion of bupropion through human cadaver skin when used as plasticizers. Incorporation of succinic acid in the adhesive matrix retarded diffusion due to the formation of rigid cross linking of the polymer, while propylene glycol and myristic acid, alone or in combination, significantly enhanced the flux of bupropion through human cadaver skin.