An experimental biodegradable bone cement [poly(propylene fumarate)-methylmethacrylate] (PPF-MMA) has been compared in vivo with polymethylmethacrylate (PMMA) as a carrier agent for local release of antibiotics. This approach is potentially applicable to the treatment of chronic osteomyelitis where the clinical goal is to achieve sustained high concentrations of antibiotics locally in the infected bone. In our experiments, gentamicin- and vancomycin-impregnated cylindrical PMMA and PPF-MMA cement specimens were implanted subcutaneously in rats, and blood and wound fluid samples were obtained over a 2-week period. Antibiotic levels were determined using immunoassays, and microbiologic activity was confirmed with agar diffusion techniques. The biodegradable PPF-MMA cement achieved and maintained considerably higher wound antibiotic levels than did PMMA cement. Vancomycin levels for the PPF-MMA cement were greater than 20 times those for the PMMA cement at all sampling times from 24 h to 14 days. For both cements, the serum antibiotic concentrations remained safely below maximum levels recommended for parenteral therapy. Mechanical testing of the PPF-MMA cement showed that admixture of 3% by weight of antibiotic did not adversely affect material properties. We conclude that this experimental biodegradable bone cement (PPF-MMA) can be used as a carrier to achieve high sustained local levels and low serum levels of antibiotics. Because it is biodegradable and thus does not require a secondary procedure for removal, it has special potential for use in treatment of chronic osteomyelitis.