The aseptically loosened prosthesis provided a means for investigating the in vivo and in vitro activity of the cells associated with the loosening process in seven dogs. The cells were isolated and maintained in culture for sufficient periods of time so that their biologic activity could be studied as well as the effect of different agents added to the cells in vivo or in vitro. The biologic response as determined by interleukin-1 and prostaglandin E2 activity paralleled the roentgenographic appearance of loosening and the technetium images and observations made at the time of revision surgery. The correlation between clinical, roentgenographic, histologic, and biochemical loosening indicates that the canine model is suitable for investigating the mechanisms of prosthetic failure. A canine model permits the study of possible nonsurgical therapeutic interventions with the ultimate hope of stopping or slowing the loosening process.