C5‐normal B10.D2/new line mice were susceptible to passively transferred arthritis from purified type II collagen antibody, and in vitro studies demonstrated that, when bound to cartilage, this antibody readily activated complement C5 to C5a. C5‐deficient B10.D2/old line mice failed to develop passively transferred arthritis, despite the deposition of antibody and C3 along the cartilage surface. C57B1/6 mice were susceptible to passively transferred arthritis, which was characterized in histopathologic studies as an erosive synovitis involving multiple inflammatory cell types. In contrast, neither clinical nor histologic evidence of arthritis was observed in C57B1/6 mice with the beige mutation (Chediak‐Higashi syndrome).