We studied the immune system in 18 cases of Behçet's disease with ocular involvement. The proportion of CD69+ cells in CD4+ cells was significantly higher in patients with active uveoretinitis than in normal controls (p < 0.01). After OKT-3 stimulation of cultured cells, the proportion was significantly increased in controls (p < 0.01) but not in patients. Fas-ligand positive cells in CD8+ cells in patients did not increase after OKT-3 stimulation. Thus, the T cells in patients were in an activated state in vivo but were not further activated by OKT-3 stimulation. Cultured lymphocytes of patients after OPT-3 activation and anti-Fas antibody stimulation showed that the T cells in the active stage of the disease were resistant to apoptosis and unlikely to undergo regression by activation-induced cell death (AICD). The mean level of soluble Fas antigen was significantly elevated in sera of patients with active uveoretinitis as compared with normal controls (p < 0.05). TdT-mediated dUTP-biotin nick end labelling (TUNEL)-positive infiltrating cells were present in the inflamed retina and the posterior chamber in experimental autoimmune uveoretinitis (EAU) in rats, suggesting the involvement of apoptosis of infiltrated cells in the regression of inflammation. Serum concentration of tumor necrosis factor-alpha (TNF-alpha) was significantly elevated after 9 days of immunization in rats (p < 0.02). The inflammation score was suppressed by intravenous administration of anti-TNF-alpha antibody from days 7 to 14. It is concluded that intraocular inflammation in Behçet's disease is associated with activation of T cells and abnormality in apoptosis and AICD mechanisms. Systemic anti-TNF-alpha antibody promises to be of value in the treatment of the disease.