Spherical monolithic microspheres, with a honeycomb-like internal architecture, composed of PLCG 50:50 and PLCG 75:25 and containing a range of vancomycin loadings, have been fabricated using a W/O emulsification with solvent evaporation technique. Microspheres were generated in high yield (80 wgt%) and vancomycin incorporation, confirmed using the displacement of DSC thermograms, had no significant effect on microsphere size distribution (5-50 mu m). The vancomycin encapsulation efficiency was high (>64%) and release profiles were characterized by a substantial initial burst release and a subsequent low-level sustained release extending up to 30 days depending upon the fabrication polymer, % vancomycin loading and incubation medium used. In both Hank＇s buffer and newborn calf serum the mean total cumulative release of vancomycin from microspheres increased significantly with theoretical percentage loading.