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Although particulate debris has been implicated as the major type of implant debris mediating macrophage\u2010induced osteolysis, the degree to which metal ions affect a proinflammatory response (if at all) remains unknown. We hypothesized that both soluble and particulate metal implant debris will induce proinflammatory responses in human monocytes resulting in cytokine production and elevated expression of T cell costimulatory molecules, facilitating adaptive immune responses. We tested this hypothesis by characterizing the response of a human monocyte cell line (THP\u20101), isolated primary human monocytes and PBMCs challenged with Co\u2010Cr\u2010Mo alloy particles and soluble cobalt, chromium, molybdenum, and nickel ions. Our results indicate that soluble cobalt, nickel, and molybdenum can induce monocyte up\u2010regulation of T cell costimulatory molecules (CD80, CD86, ICAM\u20101) in human monocytes\/macrophages. Furthermore, cobalt, molybdenum ions, and Co\u2010Cr\u2010Mo alloy particles similarly induce elevated secretion of IL\u20101\u03b2, TNF\u03b1, and IL\u20106. Antibody blockade of CD80 and CD86, crucial secondary molecules for adaptive responses, abrogated lymphocyte reactivity to metal challenge in metal reactive subjects. Also the addition of IL\u20101 receptor antagonist (IL\u20101ra), (which indirectly blocks pro\u2010IL\u20101\u03b2 and thus IL\u20101\u03b2 release), significantly reduced lymphocyte reactivity in metal\u2010reactive subjects. Thus, both soluble and particulate metal implant debris induce monocyte\/macrophage proinflammatory responses that are metal and individual specific. This suggests metal\u2010induced up\u2010regulation of costimulatory molecules and proinflammatory cytokine production is necessary to induce lymphocyte activation\/proliferation to metal implant debris. \u00a9 2009 Wiley Periodicals, Inc. 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