Titanium alloy particles were isolated from membranes obtained at revision arthroplasty. Addition of these retrieved particles to human monocytes/macrophages in cell culture resulted in morphologic change and metabolic activation. Cells exposed to these particles actively phagocytized the metallic debris, resulting in an increase in cytoplasm and a polarization of ingested metal. The metabolic response of the macrophages included increased release of prostaglandin E2, interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha, and increased hexosaminidase activity. Increased release of interleukin-1 beta was maximal 6 to 12 hours after particle exposure. These data show that retrieved titanium alloy particles activate macrophages in vitro in an analogous fashion to that observed around failed arthroplasties.