The objective of this work was to evaluate various methods of sustained delivery to achieve therapeutic intravitreal levels of ciprofloxacin as a potential therapy for endophthalmitis. Two types of intravitreal bioerodible sustained release devices of ciprofloxacin were evaluated in vitro. The most promising device was evaluated in rabbits and results compared with subconjunctival injections of a ciprofloxacin suspension. Subconjunctival injections failed to deliver therapeutic concentrations of ciprofloxacin into either the aqueous or vitreous. In vivo evaluation of the intravitreal device consistently delivered ciprofloxacin at levels above 1 ug/ml for up to four weeks. No retinal activity was noted by clinical examination or by electroretinogram. Intravitreal implantation of bioerodible ciprofloxacin devices can maintain vitreous concentrations above 1 ug/ml, more than the MIC90 of most organisms associated with endophthalmitis. Implantation of these devices appears to be well tolerated and may represent a viable treatment for this disease. Further studies in endophthalmitis models are needed to evaluate device efficacy.