This study reports the encapsulation of plasmid DNA in erythrocyte ghosts. The plasmid DNA was encapsulated into erythrocyte ghosts using three methods; osmotic shock, electroporation in isotonic medium, and e1ectroporation in hypotonic medium. Of three methods, electroporation in hypotonic medium resulted in the highest encapsulation efficiency of plasmid DNA. The morphology of erythrocyte ghosts prepared by electroporation in hypotonic medium was similar to that by osmotic shock alone. The circulation time of plasmid DNA in mice was prolonged by administration in erythrocyte ghost-encapsulated forms. These results indicated the potential of erythrocyte ghosts for biocompative nonviral delivery system of therapeutic genes for hematological diseases.