Bucillamine, an anti-rheumatic drug, was compared with cyclosporine (CYA) in its effects on the antigen-presentation activity of antigen-presenting cells (APCs) and the antigen-specific proliferation of T cells from S-antigen-immunized rats. In vitro assay showed that bucillamine did not affect the proliferative response of T cells, but suppressed the antigen-presenting activity of APCs, such as macrophages and retinal pigment epithelial cells. On the other hand, CYA suppressed both T cell proliferation and the antigen-presenting activity of macrophages. However, the doses of CYA required to produce significant suppression of antigen presentation were higher than those needed to inhibit T cell proliferation. Daily systemic administration of bucillamine for 14 days after immunizing rats with S-antigen suppressed the intensity of experimental autoimmune uveitis (EAU) and the antigen-presenting activity of macrophages in treated rats, but not the antigen-specific proliferation of the T cells. EAU intensity was completely suppressed by CYA for 14 days post-immunization, and antigen-specific proliferation of T cells was suppressed, but the antigen-presenting activity of macrophages was not affected. These results suggested that the suppressive effects of bucillamine on the antigen-presenting activity of APCs contributed to its suppressive effects on EAU; whereas, the suppressive effects of CYA on EAU resulted principally from its suppression of the T-cell function.