Background: Cobalt/chromium alloy is the most frequently used material in knee replacement hardware. It is composed of 60% cobalt, 30% chromium, 5% molybdenum, and contains from 0.5 - 2% nickel. We have found that nickel sensitization is an important cause of failed knee replacements in these patients. Despite such low percent concentrations in the alloy, whether nickel elutes from the implant material and become detectable in synovial fluid from cobalt/chromium knee replacements has never been measured. If so, such soluble material would be more available to trigger an immune inflammatory response. Methods: After obtaining written informed consent, we collected synovial fluid from the knees of patients with failed cobalt/chromium knee replacements, from those with other non-nickel containing implants, or those without implants with osteoarthritis or rheumatoid arthritis. We measured synovial fluid concentrations of nickel, cobalt, chromium, and molybdenum by inductively coupled plasma-mass spectrometry (ICP-MS). Results: Nickel and cobalt concentrations were significantly higher in patients with cobalt/chromium knee replacements, and virtually non-detectable in other non-nickel, non-cobalt implants or in other causes of knee arthritis. In those with failed cobalt/chromium knee hardware, nickel concentrations were also significantly higher in patients with failure due to nickel sensitization compared to those with other causes of failure. Conclusion: Despite low concentrations in cobalt/chromium alloy, nickel does elute from this material, is detectable in synovial fluid from failed cobalt/chromium knee replacements, and is significantly higher in nickel-sensitized patients with these failed implants. Elevated cobalt concentrations are also found in some of these patients.