We investigated the effect of the polymer-drug interaction on the surface morphology of polymer microspheres and in vitro release properties. Polylactide microspheres enclosing the antitumor agent Irinotecan hydrochloride (CPT) were prepared by the solvent evaporation method of the O/O emulsion system in order to control the concentration of drugs in living organisms. The mean diameter of the polylactide microspheres was kept at approximately 50 mum while varying the content of CPT. The enclosing efficiencies in all runs were around 80%, independent of the CPT content. The surface morphology of polylactide microspheres was significantly affected by the content of the enclosing CPT. Furthermore, the degree of unevenness of the surface was increased with an increase in the CPT content in polylactide microspheres. DSC studies have suggested that the glass transition temperature of polylactide microspheres enclosing CPT shifted to lower temperatures with an increasing CPT content. It was assumed from DSC measurements that the morphological change of polylactide microspheres was induced by a polymer-drug interaction. In vitro release experiments suggested that the release rate in the early period increased with an increasing CPT content. From this study, it was pointed out that the drug, miscible with the matrix polymer, induced a change in surface morphology, providing a significant effect on release properties.