High levels of cobalt and chromium ions are detected in the blood and urine of patients with metal-on-metal (MOM) hip replacement despite, even with these elements are released as a result of wear at the bearing surfaces. The clinical effects of elevated metal ion levels include local tissue reactions, characterized by increases in T and B cells in the tissues surrounding the hip, and are associated with premature failure of the hip. Systemically, one report suggests reduced numbers of CD8-positive T cells. Metal sensitivity is also a potential problem. Metal ions, whether produced secondary to wear debris or via corrosion can initiate a hypersensitivity response. A delayed cell-mediated response, or delayed-type hypersensitivity response can occur, in which cytokines are released by T-lymphocytes and increased activation of macrophages is seen, which may result in T-cell mediated periprosthetic osteolysis. Many metals can initiate a hypersensitivity response, the most common is nickel followed by cobalt and chromium. Therefore, with the well-documented elevation of cobalt and chromium ions in patients with MOM hip implants, there is a theoretical risk of developing hypersensitivity reactions. Recently, an immune response exclusively associated with second-generation MOM hip prostheses, has been described. Histomorphological changes suggest a type of hypersensitivity reaction to the all-metallic implants. The hypersensitivity hypothesis was further strengthened by the observation that these patients experienced early clinical failure at 11-60 months (mean 29 months), and the fact that patients who received a second MOM prosthesis did not experience any relief of symptoms. Conversely, patients who received either metal-on-polyethylene or ceramic-on-polyethylene couples reported that their symptoms completely disappeared. In a control group of patients with joint prostheses not containing cobalt, chromium or nickel these signs of an immunological reactions were absent. Reports of this type of reaction are becoming increasingly common; however, more research is needed in this area. It is not known whether these patients experience prosthesis failure because of a pre-existing metal sensitivity, or whether metal sensitivity develops because of a high wearing bearing and elevated metal ion levels. Theoretically, there would be an increased probability of developing hypersensitivity to elevated metal ion levels, and hence an increased risk of implant failure.