Biochemical and histologic analyses were performed on interface membranes obtained at revision of aseptically loosened hip implants (n = 36) and knee implants (n = 16). Clinical failure occurred sooner in patients with uncemented total hip implants (Group 1) than in patients with cemented implants (Group 2) (p < 0.02). There was no difference in time to revision between the patients with uncemented implants (Group 3) and patients with cemented total knee implants (Group 4). Histologically, more small (< 5 mu) polyethylene particles were found within macrophages and fibroblasts in membranes from Groups 1 and 2. Polyethylene particles from failed total knees (> 10-100 mu) were larger than those from failed total hips. Large polyethylene fragments and foreign-body giant cells were more common in failed knees than failed total hip membranes. Biochemically, proteinase and cytokine activity in the tissue culture supernatant from all groups was higher than in the control tissue (p < 0.01). The activities of stromelysin, prostaglandin E2, interleukin-1 alpha, interleukin-1 beta, and tumor necrosis factor-alpha were higher in Groups 1 and 2 than in Groups 3 and 4 (p < 0.05). These findings support the hypothesis that interface membranes enveloping femoral (hip) and tibial (knee) components of failed total joint implants may promote bone resorption and aseptic loosening. The reason for slower failure of knee implants as compared with hip prostheses may be the lower level of biochemical activity and macrophage density that correlates closely with larger polyethylene particles.