To achieve a therapeutical effect of the anti-Parkinson's drug R-apomorphine via iontophoresis delivery, enhancement strategies in vitro were explored using three structurally related enhancers, lauric acid (LA), dodecyltrimethylammonium bromide (DTAB) and Laureth-3 oxyethylene ether (C(12)EO(3)). Human stratum corneum and shed snake skin were pretreated with 0.15 M each enhancer solution in propylene glycol (PG). Thereafter, passive diffusion, iontophoretic transport and post-iontophoretic passive diffusion were investigated. Compared to the control (PG pretreatment), a slight inhibition on both passive and iontophoretic delivery was observed with cationic surfactant DTAB pretreated stratum corneum. Pretreatment with anionic surfactant LA resulted in a great enhancement on passive delivery, but only a small enhancing effect on the iontophoretic delivery. Unlike the others, the nonionic surfactant C(12)EO(3) substantially increased iontophoretic transport rate of R-apomorphine by 2.3-fold, whereas passive delivery was basically unchanged or slightly affected. The magnitude of enhancing effect of C(12)EO(3) was dependent on the surfactant concentration and the pretreatment duration. Moreover, comparison of transport data through shed snake skin with human stratum corneum indicates that both shunt- and intercellular pathways are involved in the iontophoretic transport of R-apomorphine.