In aseptic loosening of initially well inserted total hip prosthescs, implant wear debris and cyclic mechanical loading lead to a foreign body type of chronic inflammatory reaction, then to osteolysis, and finally to loosening of the implant. In the present work the reactive and adaptive changes of the periprosthetic tissues and pseudojoint were characterized by analysis of the local cell proliferation. Immunohistochemical demonstration of proliferating cells was performed by application of affinity purified rabbit antihuman Ki-67 antibodies to periprosthetic tissues obtained from revision operations for loose total hip prostheses. The fibrous areas and, in particular, the cell rich, vascular areas of the interface tissue (between implant and bone) and the pseudocapsule around aseptically loosened implants contained higher numbers of proliferating cells than the tissues around well fixed implants. In addition, the pseudosynovial lining occasionally contained some Ki-67 positive proliferating cells. Somewhat surprisingly, proliferating vascular endothelial cells were relatively rare. These findings suggest that reactive (interface tissues) and adaptive (pseudojoint and capsule formed around the artificial joint) tissue changes in loosening total hip prostheses comprise proliferation of local fibroblastlike cells. It is concluded that periprosthetic tissues of the loosened total hip prosthesis represent activated mesenchymal tissue.