The aim of this study was to investigate the cathodal iontophoresis of dexamethasone sodium phosphate (DEX-P) in vitro and in vivo and to determine the feasibility of delivering therapeutic amounts of the drug for the treatment of chemotherapy-induced emesis. Stability studies, performed to investigate the susceptibility of the phosphate ester linkage to hydrolysis, confirmed that conversion of DEX-P to dexamethasone (DEX) upon exposure to samples of human, porcine and rat dermis for 7h was limited (82.2±0.4%, 72.5±4.8% and 78.6±6.0% remained intact) and did not point to any major inter-species differences. Iontophoretic transport of DEX-P across dermatomed porcine skin (0.75mm thickness) was studied in vitro as a function of concentration (10, 20, 40mM) and current density (0.1, 0.3, 0.5mAcm −2 ) using flow-through diffusion cells. Increasing concentration of DEX-P from 10 to 40mM resulted in a ∼4-fold increase in cumulative permeation (35.65±23.20 and 137.90±53.90μgcm −2 , respectively). Good linearity was also observed between DEX-P flux and the applied current density (i d ; 0.1, 0.3, 0.5mAcm −2 ; J DEX (μgcm 2 h −1 )=237.98 i d −21.32, r 2 =0.96). Moreover, separation of the DEX-P formulation from the cathode compartment by means of a salt bridge – hence removing competition from Cl − ions generated at the cathode – produced a 2-fold increase in steady-state iontophoretic flux (40mM, 0.3mAcm −2 ; 20.98±7.96 and 41.82±11.98μgcm −2 h −1 , respectively).Pharmacokinetic parameters were determined in Wistar rats (40mM DEX-P; 0.5mAcm −2 for 5h with Ag/AgCl electrodes and salt bridges). Results showed that DEX-P was almost completely converted to DEX in the bloodstream, and significant DEX levels were achieved rapidly. The flux across rat skin in vivo (1.66±0.20μgcm −2 min −1 ), calculated from the input rate, was not statistically different from the flux obtained in vitro across dermatomed porcine skin (1.79±0.49μgcm −2 min −1 ). The results suggest that DEX-P delivery rates would be sufficient for the management of chemotherapy-induced emesis.