To analyze the pathogenesis of Behçet's disease (BD), we investigated the immune response of peripheral blood T cell subsets from patients with BD to Streptococcus sanguis (S. sanguis) strain KTH-I, a bacteria suggested to be associated with the etiology of BD. Cultured peripheral blood mononuclear cells (PBMC) of patients with BD activated by lyophilized whole bacterium of S. sanguis were assayed by two-color flow cytometry using monoclonal antibodies (mAbs) specific for gamma delta+ T cell receptor, CD4 or CD8 molecules. The lymphostimulatory activity of S. sanguis to either gamma delta+ CD4-CD8-, gamma delta+ CD4-CD8+, gamma delta-CD4+CD8-, or gamma delta-CD4-CD8+ T cells was evaluated. The absolute number of gamma delta+ T cells from patients with BD (n = 8) as well as from healthy controls (n = 7) significantly increased after stimulation with S. sanguis, whereas gamma delta- T cells from both groups showed no response to S. sanguis. The absolute number of gamma delta+ CD8+ T cells from patients with BD significantly increased after stimulation with S. sanguis compared with healthy controls (p < 0.05). Peripheral gamma delta+ CD8+ T cells from patients with BD showed a significantly higher proliferative response to S. sanguis compared with healthy controls.