Systemic sodium fluoride has been used in the treatment of osteoporosis. Recent studies have shown that it has a positive risk/benefit ratio for use in increasing spinal trabecular bone density. However, thinning of the cortices of the long bones with a resulting increase in fracture incidence has been observed. This study was designed to determine the response of bone to sodium fluoride released from a biodegradable polymer matrix, a technique which could potentially deliver it locally to a site of need in the skeleton which has a positive response to fluoride. In one group of mature New Zealand white rabbits, cylindrical poly(D,L-lactic acid) (PLA) implants, with or without impregnated sodium fluoride, were implanted into the contralateral femoral trochanters and tibial metaphyses. In a second group, similar implants were placed in adjacent vertebrae. Four weeks postimplantation, the femora, tibiae, and vertebrae were removed, sectioned, cleaned of all but mineralized tissue, and the surfaces of the sections stained. The stained surfaces were imaged and analyzed for morphometric properties of the trabeculae. Comparing contralateral vertebrae, those exposed to sodium fluoride had significantly thickened trabeculae, with decreased spacing between them and a greater bone fraction. A similar increase in trabecular width was found in the subchondral bone of the proximal tibiae exposed to local release fluoride. Femoral sections showed no difference, possibly due to the lack of extensive trabecular bone in the region chosen for study.