Starch is a natural polymer that is among the sustainable materials and has the characteristics of being a green material in harmony with nature. In this study, a potential transdermal release system was evaluated by investigating 5-fluorouracil (5-FU) transfer through starch/poly(vinyl alcohol) (PVA) membranes in vitro. The effects of membrane thickness, starch/PVA blending ratio, pH, and temperature on the release of 5-FU from the membranes were studied. At the end of the study, it was deduced that decrease in pH reduces the released amount of 5-FU from starch/PVA membranes and 5-FU transfer from membranes could be controlled within a fairly constant range. The diffusion coefficient was determined as 4.84x 10(-3), 4.49x 10(-3) and 2.54x 10(-3) cm(2) s(-1) for the pH of 7.4, 5.5, and 3.5, respectively. The activation energy for the permeation 5-FU from starch/PVA membrane (60/40, v/v) was found to be 9.72 kJ mol(-1).