Greater attention has been recently paid to the role of certain strains of streptococcus as an etiologic agent of Behçet's disease, in which T cell abnormalities are considered to be involved. We therefore examined whether T cells from patients with Behçet's disease might to be stimulated by Streptococcus sanguis-related antigen (RRE KTH-1 antigens). T cells from 17 patients with Behcet's disease, but not those from 13 healthy individuals or from 13 patients with other rheumatic diseases, were stimulated to produce greater amounts of interleukin 6 (IL6) by addition of RRE KTH-1 antigens [stimulation index: 3.96 +/- 0.56 and 1.35 +/- 0.28 or 1.83 +/- 0.43 (mean +/- SEM), respectively]. The IL6 production by T cells required the presence of either fresh or paraformaldehyde-fixed monocytes. The enhancement of T cell IL6 production was not related to the presence of HLA-B51, which has been shown to be frequently associated with Behçet's disease. These results indicate that T cells from patients with Behçet's disease are stimulated by streptococcal antigens to produce IL6 through T cell-monocyte interactions in which binding of the antigens to monocytes, but not necessarily processing of the antigens by monocytes, is involved. Moreover, RRE KTH-1 antigens as well as Escherichia coli-derived antigens also enhanced the production of interferon-gamma by T cells from patients with Behçet's disease. The data thus suggest that T cell hypersensitivity to several bacterial antigens may play a central role in the pathogenesis of Behçet's disease.