Topical delivery of cyclosporin A (CSA) is desirable for treating psoriasis, but it is hindered by the barrier property of stratum corneum, and the physicochemical properties of CSA. Attempts to deliver CSA from a solution prepared in 40% ethanol (EtOH) in phosphate buffered saline (PBS) using iontophoresis did not result in any significant increase in drug delivery, compared to passive. However, the use of electroporation pulses as a physical penetration enhancer enabled delivery of a significant amount of CSA. Single pulse electroporation study indicated that the amount of EtOH delivered across the skin increased as the applied electrode voltage (U-electrode) was increased. However, it did not translate into a proportional increase in the delivery of CSA and only a three to four times increase, compared to passive delivery, was seen with the single pulse electroporation. The drug contact duration had a varying effect in the efficiency of transdermal delivery of CSA. Four hour contact duration was chosen for the multiple pulse study. Use of multiple pulses (25 pulses, 10 ms each) at U-electrode 200 V resulted in a sixty-fold increase, compared to passive, in the delivery of CSA to the skin. Transdermally delivered CSA was mostly bound to the skin and only a small amount was seen to cross the full skin into the receiver compartment. In a study of solvent transport, the flux of water was up to three times larger than that of EtOH after electroporation. (C) 1998 Elsevier Science B.V.