Protein binding of drug is responsible of ineffectiveness of conventional hemodialysis. The aim of the present study was to investigate the potential of electrodialysis, i.e. the transport of charged solutes through a membrane under the influence of an external electric potential, to increase the clearance of phenytoin, i.e. a model albumin-bound drug from human serum in vitro. Electrodialysis was performed through cellulose triacetate membrane mounted onto electrodialyser built in-house which separated: (a) saline solution, (b) 4% albumin saline solution or (c) human serum and dialysate compartments. The electric current density between both electrodes placed into donor (cathode) and dialysate (anode) compartments was settled to 0.79 mA/cm(2) for 3 h at 37 degreesC. Recovery of phenytoin in dialysate from either (a) saline solution or (b) 4% albumin saline solution was significantly higher than that obtained by classical dialysis ((a): 42% versus 24%; (b): 30% versus 6%). In human serum, the effectiveness of electrodialysis was appreciated by the unbound phenytoin clearance, which was about twice higher than in dialysis (0.22 ml/h versus 0.12 ml/h). However, the removed fraction of 10% in the human serum could just reflect the usual unbound phenytoin. Consequently, the impact of electrodialysis on the protein binding was not affirmed, but the ability of this technique to eliminate shortly free drug was clearly demonstrated. Electrodialysis would be a promising improvement of hemodialysis for the elimination of ionized drugs from human blood.