In this paper we report that intraperitoneal administration of type II collagen in a soluble form protects DBA/1 mice against collagen-induced arthritis (CIA) on subsequent arthritogenic challenge with soluble type II collagen in adjuvant. The degree of arthritis suppression, which is expressed in terms of reduced incidence of arthritis, delayed onset and reduced anti-collagen antibody titres, depends on the dose and timing of the pre-immunization collagen injection. In order to elucidate the rôles of CD4+and CD8+T lymphocyte subsets in arthritis resistance we administered monoclonal antibodies (mAb) to these antigenic determinants around the time of immunization with soluble type II collagen. Anti-CD4 mAb caused abrogation of arthritis resistance while anti-CD8 mAb was less effective. However, administration of anti-CD8 mAb two weeks after pre-immunization with soluble collagen was very effective in reversing arthritis resistance. From these findings we conclude that CD4+and CD8+T cells are involved in resistance to arthritis though the relative importance of each subset changes during the course of the process leading to resistance to CIA.