Iontophoresis is a non-invasive technique which applies a mild electric current to enhance the penetration of molecules into and through tissues. It can be used for the transdermal delivery of drugs with low oral bioavailability since it avoids both first-pass metabolism and degradation in the gastro-intestinal tract. However, many polar molecules with good aqueous solubility do not cross the lipophilic stratum corneum, the principal rate-limiting barrier of the skin, in sufficient amounts for a therapeutic effect. To overcome this problem, impairment of the skin has been proposed in conjunction with iontophoresis. Since iontophoresis acts principally on the permeant, barrier impairment may offer some degree of synergy. However, some questions still remain: When this rate-limiting membrane is absent or impaired, how are the electrical properties of the skin modified? The contribution of passive transport is expected to increase – but how does barrier integrity affect electrotransport, which is governed by the permselective nature of the rate-limiting membrane? The aim of this project is to answer these questions by investigating the effect of molecular properties on iontophoretic transport across different impaired skin barriers.