Various bupivacaine-loaded microsphere systems have been prepared from polylactide-co-glycolide (PLGA) and from blends of different molecular weight polylactide (PLA) by a solvent evaporation-extraction method. In vitro drug release profiles displayed significant differences between polymers. Among PLA microspheres, the initial release was accelerated with increasing proportion of low molecular weight PLA. Preliminary pharmacokinetic studies following intrathecal and intraperitoneal administration of different bupivacaine-loaded microspheres in rabbits illustrated the controlled release of this drug.