Twenty monoclonal antibodies reactive with type II collagen were characterized as to their determinant specificity and their reactivity with cartilage-derived components. The monoclonal antibodies reacted with 7 different epitopes on the native type II collagen triple helical structure. Antibodies defining 3 of these epitopes occurred more frequently in sera from arthritic mice than in sera from nonarthritic mice. In vivo injection of some selected autoreactive antibodies caused synovitis, but in no case did it give rise to full-blown arthritis.