A novel biphasic transdermal drug delivery system was developed to provide a technology of varying the temporal rate of the drug input to optimize the chronopharmacological response. The biphasic profile of a drug across skin was obtained by using a permeation enhancer to provide a high initial flux, and a subsequently lower flux by the rapid depletion of the enhancer from a finite volume reservoir. A pseudo-steady-state model was developed to guide the formulation and the design of this system. The performance of a nitroglycerin biphasic transdermal system was demonstrated in vitro, using aqueous ethanol as an enhancer.