High fluid pressures can be present throughout the effective joint space after total hip replacement and can extend locally to the bone implant interface. A new experimental implant model was developed to study whether local fluid pressure can induce osteolysis at a bone implant interface. Twelve mature rabbits received a titanium implant that was allowed to osseointegrate before a fluid pressure of 150 mm Hg was applied to a specific area of the titanium bone interface in six of the animals. Osteolysis occurred in all six implants exposed to the fluid pressure. In two of these animals, no measurable flow occurred. In both animals a localized osteolytic lesion developed with evidence of osteocyte death in the surrounding cortical bone. In four animals, fluid flow away from the lesion occurred after several days that corresponded to either the formation of a canal through the cortical bone or extended re-sorption of the surrounding cortical bone. In some of these specimens, the microscopic appearance was similar to that of prosthetic loosening: high numbers of macrophages were observed containing intracellular bone particles. No resorption was found in any of the six control animals. The authors' results point to the possibility that all features of prosthetic loosening that are ascribed to particle activation can be explained alternatively by effects of fluid pressure.