The transdermal iontophoretic delivery of the reproductive peptide hormone, luteinizing hormone releasing hormone (LHRH) is investigated in the isolated perfused porcine skin flap model (IPPSF). LHRH is delivered twice in a single flap experiment in efforts to identify factors inherent to iontophoretic delivery that might effect the drug flux of a subsequent iontophoretic episode. Initial iontophoretic delivery of LHRH is quite reproducible; however, subsequent iontophoretic episodes result in widely divergent fluxes thought to be caused by iontophoretic influences on the skin. Iontophoretic application of a drug on a previous active site, enhances the flux during the second application. A mass balance study is performed to explain these findings. By iontophoretically delivering I125 labelled LHRH in the isolated perfused porcine skin flap model, the entire iontophoretic dose is identified and quantified. A drug depot is identified in the skin underlying the electrode which is approximately two times as large as the entire mass of drug delivered systemically.