Biochemical, histological, and immunohistochemical studies of interface membranes surrounding failed hip prostheses that had been inserted without cement were done to examine specific factors involved in the development of aseptic loosening. Membranes from sixty-four femoral components were obtained from sixty-three patients during revision arthroplasty. Fifty-seven membranes were from implants that articulated with polyethylene (thirty-two were made of cobalt-chromium alloy and twenty-five, titanium alloy), and seven were from unipolar endoprostheses made of cobalt-chromium alloy that did not articulate with polyethylene. The membranes from implants with a polyethylene articulation produced significantly higher levels of collagenase and interleukin-1 (p < 0.05). However, there was no significant difference in the levels of prostaglandin E2 between the three groups. Furthermore, membranes from implants with roentgenographic evidence of focal osteolysis (endosteal erosion) released significantly higher levels of interleukin-1 (p < 0.05) than did membranes from implants without focal osteolysis. Although the membranes from the titanium-alloy implants tended to contain more metal debris than those from the cobalt-chromium-alloy implants, the biochemical findings were not significantly different between these two groups. Many macrophages that were filled with polyethylene and metal debris were present in the membranes from both groups with a polyethylene articulation. Few T lymphocytes or B lymphocytes were identified in the three groups.