Gammadelta T-cells participate in the immune response to infections and in autoimmunity by recognizing bacteria-derived and autologous antigens. The goal of this study was to evaluate the involvement of gammadelta T-cells in Behçet's disease (BD). Gammadelta T-cells in the peripheral-blood mononuclear cells (PBMCs) of Israeli patients with definite BD (n = 23), normal controls (n = 16), and patients with familial Mediterrranean fever (FMF; n = 20) were evaluated by means of flow cytometry. The responses of patient and control gammadelta T-cells to medium conditioned by microorganisms cultured from an oral ulcer of a patient with active BD were compared. The proportions of CD3(+) and CD8(+) cells in the PBMCs were not significantly different between groups. In contrast, gammadelta-T-cells accounted for 7.01% +/- 4.42% of the PBMCs in BD compared with 3.56% +/- 3.45% in FMF (P < .005) and 3.7% +/- 3.15% in normal individuals (P < .009). Their numbers were significantly higher during active disease than in remission (9.45% +/- 5.08% versus 2.27% +/- 3.3%; P < .009). The number of T-cell-receptor gammadelta(+) and Vdelta2(+) cells of BD patients, but not of controls, increased after 96 hours of culture in medium containing supernatant of microorganisms cultured from an oral ulcer in a patient with BD relative to their proportions in control medium: 58.2% vs 13.9% (P < .05) and 28% vs 9% (P < .04), respectively, of the cultured T-cells (n = 4).gammadelta T-cells are expanded in BD PBMCs during active disease. An exaggerated proliferative response to products released by microorganisms present in oral ulcers may play a role in this phenomenon.