Administration of oestrogen to castrated female rats has previously been shown to exert a suppressive effect both on the development of collagen-induced arthritis (CIA) and on the delayed-type hypersensitivity (DTH) reaction to collagen II (CII). The present study is concerned with the mechanisms responsible for this suppression, particularly as to the role of the thymus and the CD8+ T lymphocytes; both the thymic epithelial cells and the CD8+ T cells have earlier been implicated as responsible for oestrogen-mediated immunomodulation on the basis of their expression of oestrogen receptors. Adult thymectomy alone did not affect either the incidence or severity of arthritis. Furthermore, adult thymectomy did not change the observed suppressive effects of oestrogen treatment on arthritis development or auto-anti-CII T-cell immunity. Elimination of CD8+ T cells was subsequently achieved in groups of thymectomized rats by utilizing the fact that efficient depletion of CD8+ T cells occurs after in vivo treatment with OX8 monoclonal antibodies; depletion of peripheral CD8+ T cells failed to influence the suppressive effect of oestrogen on CIA and on the in vitro proliferative response of lymph-node cells to CII. Depletion of CD8+ T cells did, however, in itself reduce the incidence of CIA in non-oestrogen-treated and thymectomized rats. We conclude that oestrogen may exert its suppressive effect on development of CIA and on T-cell responsiveness via mechanisms independent of both the thymus and the CD8+ T-cell subpopulation, but that CD8+ T cells are nevertheless involved in the regulation and/or effectuation of the immune reactions responsible for development of collagen arthritis in rats.