The re-introduction of metal-on-metal joint replacements and their subsequent poor performance has increased interest in the biological response to metallic debris, particularly metal hypersensitivity and its relationship to osteolysis. Since the immune response is implicated in some implant failures, it is possible that other immune irregularities, such as rheumatoid arthritis, can affect survival of implants. For this study, chromium hypersensitivity was induced in one group of DBA/1 mice, collagen induced arthritis was induced in another group, and a control group was sensitized to keyhole limpet hemocyanin, an irrelevant antigen. All mice then received air pouches with syngeneic bone implanted. Antibodies to chromium and collagen were measured to assess sensitization, and arthritis progression was assessed daily. The animals were divided into three groups, receiving saline, polyethylene, or cobalt-chromium particles injected into the pouch. The mice were sacrificed 26 days after particle injection. Pouch thickness, cell count, inflammation, lymphocyte infiltration, and bone density were assessed histologically. The inflammatory responses differed based on the type of biomaterial, regardless of immunological sensitization. Polyethylene was consistently the most inflammatory debris. There were no significant differences in lymphocytic infiltration or bone resorption between groups. High variability was observed in responses, with some mice exhibiting little inflammation and lymphocytic infiltration and others showing severe inflammation and perivascular lymphocytic cuffing. Neither biomaterial appeared to alter the course of the arthritis. Individual responses to immunological stimuli and inflammatory debris are complex and resulted in variability within the experimental groups. This finding mirrors the patient experience, but hinders investigations of precise factors affecting adverse biomaterial responses. The dominant responses to biomaterial debris were inflammatory, even in the presence of adaptive immunological sensitivity. Based on this research, rheumatoid arthritis is not expected to elicit biomaterial concerns during joint replacement surgery.