The long-term effects of cobalt-chrome alloy prosthesis wear particles were studied using intraarticular injection of particles into rat knees and killing the rats at regular periods from 1 week to 2 years following injection. The initial response was synovial ulceration, macrophage infiltration, and necrosis. A transient lymphocyte response was present at 1 week. Fibrosis of the subsynovium occurred subsequently at the sites of necrosis. A semiquantitative assessment of the number of particles and macrophages in the synovium demonstrated that the distribution of particles did not alter during the period from 1 week to 1 year. The macrophage response decreased between 1 and 2 weeks and then remained constant for 1 year. No tumors developed. This study emphasizes that cobalt-chrome wear particles and the associated macrophage response persist in the tissues for up to 2 years. The findings are relevant to the effects of wear of all designs of cobalt-chrome alloy prostheses.