DBA/1 mice develop systemic polyarthritis and high titres of collagen autoantibodies after immunization with type II collagen. In this study we have analysed the frequency and specificity of antibody-producing B cells in draining lymph nodes 11 days after a primary immunization with rat type II collagen. A remarkably high frequency of type II collagen-reactive hybridomas (30%, n = 71), the majority cross-reacting with autologous type II collagen, were generated. Most of the collagen-reactive hybridomas produced IgG antibodies specific for type II collagen. Many other hybridomas produced multispecific antibodies (9%): these were preferentially of the IgM class. Some of the monoclonal multispecific hybridomas produced antibodies that cross-reacted with specific epitopes on the collagen molecule. One type II collagen-reactive hybridoma also displayed rheumatoid factor activity. Different mechanisms for the generation of the high frequency of collagen reactive antibodies are discussed.