Monoclonal anti-idiotypic antibodies previously shown to react with a cross-reactive idiotope of anti-collagen II auto-antibodies were used for in vivo treatment of DBA/1 mice receiving immunization with arthritogenic native rat collagen type II. Injection of 100 micrograms of the anti-idiotypic antibody 3 weeks before the collagen immunization resulted in a significant suppression of collagen arthritis, compared with mice treated with a monoclonal control antibody. The treatment with anti-idiotypic antibody 3 weeks before collagen immunization could also cause a marked down-regulation of the total serum levels of anti-collagen II antibodies. When the anti-idiotypic antibodies were administered near the time for induction of arthritis (2 days after collagen immunization) a significant effect was seen on the collagen arthritis, but not on the levels of anti-collagen antibody. As collagen-induced arthritis is a disease where both T- and B-cell mediated immunity are believed to play critical roles, the present effects of the in vivo anti-idiotype treatment on arthritis development could provide an interesting system for the study of idiotype regulation on both B- and T-cell arthritis-associated autoimmunity.