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Iontophoresis is a method of transdermal administration of ionizable drugs in which the electrically charged components are propelled through the skin by an external electric field. This study was designed to determine whether iontophoresis could be used to deliver clinically significant doses of fentanyl in humans and whether there is a charge-dose relation in the delivery of fentanyl by iontophoresis.Five adult volunteers were tested three times on separate days, once receiving passive treatment of 0.0 mA for 2 h (0 mA *symbol* min), iontophoresis 1.0 mA for 2 h (120 mA *symbol* min), and iontophoresis 2.0 mA for 2 h (240 mA *symbol* min) in an open, randomized, crossover design. Respiratory rate, heart rate, blood pressure, and hemoglobin oxygen saturation were monitored throughout the study. Plasma fentanyl concentrations were measured several times before, during, and after iontophoresis. Plasma fentanyl concentrations were measured by radioimmunoassay.No fentanyl was detected after passive (0.0-mA) fentanyl delivery. The following results were obtained for the 1.0 and 2.0-mA deliveries, respectively. Mean times to detectable concentrations of plasma fentanyl were 33 and 19 min; mean times to maximum concentration were 122 and 199 min; maximum concentrations were 0.76 and 1.59 ng/ml (P = 0.010); mean areas under the curve of the plasma fentanyl concentration versus time relation were 233 and 474 ng *symbol* ml sup - 1 *symbol* min (P = 0.003); and mean elimination half-lives were 354 and 413 min (P = 0.326). Only minor adverse side effects related to iontophoresis occurred. However, typical opioid-related effects occurred frequently in the 1.0- and 2.0-mA administration groups.Clinically significant doses of fentanyl can be administered by iontophoresis for delivery periods of 2 h. A charge- dose relation exists after administration with currents of 1.0 and 2.0 mA. Future research into the iontophoresis of fentanyl as a method of potent opioid administration is indicated.