A comparative study of plasmid DNA loading, release characteristics, and stability on polystyrene divinylbenzene and ceramic hydroxyapatite ion-exchange microspheres was undertaken. The two plasmids evaluated were pCMV-CAT and pRcCMV-p53. The effect of quantity of plasmid, temperature and alteration of the surface charge of microspheres on binding were examined. Binding correlated with the concentration of plasmid DNA available in the suspension. pCMV-CAT was bound twice as much in relation to copy number on both microspheres compared with pRcCMV-p53. Each hydroxyapatite microsphere bound 350% more plasmid than polystyrene divinylbenzene. No difference in binding was evident for either plasmid at 4, 20 or 37°C. Equilibration of both microsphere types with different salt solutions altered binding capacities when compared with that with water. In-vitro release studies revealed that 1011 copies of plasmids were being eluted from the microspheres at a flow rate of 3.0 mL h−1 of phosphate-buffered saline at 37°C. Hydroxyapatite microspheres released plasmids in a sustained manner, while polystyrene divinylbenzene microspheres released DNA in a burst. There was no plasmid degradation post-loading on to and post-release off microspheres. The present study has demonstrated that ion-exchange microspheres are capable of carrying plasmid DNA and at least in-vitro, releasing it in a sustained manner.