Previous studies have revealed that autoantibodies, complement components, and Fc receptors each participate in the pathogenesis of erosive arthritis in K/BxN mice. However, it is not known which cellular populations are responsive to these inflammatory signals. We find that two strains of mice deficient in mast cells, W/Wv and Sl/Sld, were resistant to development of joint inflammation and that susceptibility was restored in the W/Wv strain by mast cell engraftment. Thus, mast cells may function as a cellular link between autoantibodies, soluble mediators, and other effector populations in inflammatory arthritis.