Cobalt-chromium-molybdenum (CoCrMo) metal-on-metal hip prosthesis has had a revival due to their excellent wear properties. However, particulate wear debris and metal ions liberated from the CoCrMo alloys might cause carcinogenicity, hypersensitivity, local and general tissue toxicity, genotoxicity and inflammation-generating qualities. Nine months after implanting small pieces of CoCrMo alloy intramuscularly and intraperitoneally in rats, we analysed the accumulation of metals with a multi-element analysis, and the levels of metallothionein I/II with real-time reverse transcriptase-polymerase chain reaction in liver and kidney. We found that metal ions are liberated from CoCrMo alloys and suggest that they are released by dissolucytosis, a process where macrophages causes the metallic surface to release metal ions. Animals with intramuscular implants accumulated metal in liver and kidney and metallohionein I/II were elevated in liver tissue. The present data do not tell whether kidney and liver are the primary target organs or what possible toxicological effect the different metal ions might have, but they show that metal ions are liberated from CoCrMo alloys that are not subjected to mechanical wear and that they accumulate in liver and kidney tissue. That the liberated metal ions affect the tissues is supported by an up-regulation of the detoxifying/pacifying metalloprotein I/II in the liver.Second-generation metal-on-metal hip prosthesis is made by cobalt-chromium-molybdenum (CoCrMo) alloy, because it is well-tolerated and possesses excellent wear properties [1,2] (Jakobsen et al., unpublished results). The alloy consists of 62-67% cobalt and 27-30% chrome, but also includes 5-7% molybdenum and all together less than 1% of manganese, iron, nickel and silicon [3]. However, unwanted side effects could be seen as a result of the released metal ions (Cr The number of metal wear particles has been found to be 13 to 500 times higher than the number of wear polyethylene particles released from conventional hip prostheses [6,9]. The large amount of nano-metal particles and the presumed high levels of metal ions in the tissues around hip prostheses have ignited concerns of carcinogenicity [10,11] and Bouchard et al. has previously suggested a carcinogenic effect of implanted CoCrMo (ASTM F-75); however, no differences in urine, faeces and blood metal concentration were observed [16]. Epidemiological studies have shown a possible increased cancer risk, although the data until now has been inconclusive or contradictory [17][18][19][20][21][22]. Particulate wear debris has been found to accumulate in tissue close to the implant, but also in distant lymph nodes, bone marrow, liver and spleen [23], and metal ions have been shown to be excreted in the urine [4] and through the bile [24]. However, it is still not known whether released metal ions accumulate in cells of different organs [25,26].In the present study, we found that the different metal atoms present in the implants were liberated and accumulated in th...