Tissues surrounding failed conventional total hips have been shown to produce inflammatory cytokines that can induce osteoclastic bone resorption. We evaluated the cytokine profiles of tissues from 5 failed metal-on-metal total hip replacements. Serial frozen sections were stained using immunohistochemical and in situ hybridization techniques. Inflammatory and osteoclast-stimulating cytokines were noted in the tissues. As compared to a group of 5 metal-polyethylene hip tissues, we found fewer CD68 positive macrophages, and lower levels of TGF-beta and TNF-alpha, but no differences in CD3 positive lymphocytes, IL-1beta, IL-6 and PDGF-alpha in the metal-on-metal tissues. This may be due, in part to the presence of wear particles from sources other than the bearing surfaces. Thus, cytokines associated with bone resorption and implant loosening may occur in total hips despite the use of alternative bearing materials.