Aseptic osteolysis is a major complication to total joint arthroplasty requiring several thousand people a year to have to undergo revisions of their joint prosthesis. The formation of the interfacial membrane has been associated with aseptic osteolysis leading to the failure of all types of total joints. Recent evidence suggests that RANKL, a potent activator of bone reabsorption, is present in the interfacial membrane. Prior research in this laboratory to determine the source of RANKL in the interfacial membrane has revealed the presence of intense areas of RANKL concentration in the membrane. These areas of RANKL concentration correspond to multiple nuclei and a distinct cellular structure in the tissue as determined through light microscopy. This structure either represents a multi-nucleated giant cell or a cluster of cells that express high concentrations of RANKL. These following studies attempted to characterize this cell and determine its lineage.The results of these studies show that the RANIU producing anomaly appears multi-nucleated in all examples with a RANKL staining pattern that makes it appear as a multi-nucleated cell. Furthermore this RANIU positive giant cell (RPGC) stains negative for markers typically seen on myeloid cells, osteoclasts, and osteoblasts. This RPGC does however stain very well for fibroblast markers and the inflammatory cytokines TNF-α, IL-1β, and IL-6. The most interesting result from these studies revealed that this cell was positive for cytomegalovirus and expressed high concentrations of TNF-a converting enzyme (TACE). These data lead to a hypothesis as to how this cell might form and how large an impact it might play in the interfacial membrane with respect to aseptic bone reabsorption.