Poly(lactides-co-glycolides) [PLGA] are widely investigated biodegradable polymers and are extensively used in several biomaterials applications as well as drug delivery systems. These polymers degrade by bulk hydrolysis of ester bonds and break down into their constituent monomers, lactic and glycolic acids which are excreted from the body. The purpose of this investigation was to develop and characterize a biodegradable, implantable delivery system containing ciprofloxacin hydrochloride (HCl) for the localized treatment of osteomyelitis and to study the extent of drug penetration from the site of implantation into the bone. Osteomyelitis is an inflammatory bone disease caused by pyogenic bacteria and involves the medullary cavity, cortex and periosteum. The advantages of localized biodegradable therapy include high, local antibiotic concentration at the site of infection, as well as, obviation of the need for removal of the implant after treatment. PLGA 50:50 implants were compressed from microcapsules prepared by nonsolvent-induced phase-separation using two solvent-nonsolvent systems, viz., methylene chloride-hexane (non-polar) and acetone-phosphate buffer (polar). In vitro dissolution studies were performed to study the effect of manufacturing procedure, drug loading and pH on the release of ciprofloxacin HCl. The extent of penetration of the drug from the site of implantation was studied using a rabbit model. The results of in vitro studies illustrated that drug release from implants made by the nonpolar method was more rapid as compared to implants made by the polar method. The release of ciprofloxacin HCl from the implants was biphasic at =<20% w/w drug loading, and monophasic at drug loading levels =<35% w/w. In vivo studies indicated that PLGA 50:50 implants were almost completely resorbed within five to six weeks. Sustained drug levels, greater than the minimum inhibitory concentration (MIC) of ciprofloxacin, up to 70 mm from the site of implantation, were detected for a period of six weeks.