Although the etiology of Behcet's disease (BD) still remains uncertain, various immune abnormalities have been implicated in BD. We studied cytokine production in patients with active and inactive BD, and evaluated the effect of treatment with infliximab (anti-TNF-alpha antibody) on disease activity and cytokine production by the ELISPOT assay. The numbers of cells spontaneously secreting IFN-gamma, IL-12, and TNF-alpha were significantly increased in patients with active BD. Mitogen-stimulated IL-4 secretion was elevated in active patients, though the ratio of IFN-gamma:IL-4 secreting cells was significantly increased in active BD. Next, we monitored cytokine production and expression of IL-12 receptor beta1 chain (IL-12Rbeta1) during short- and long-term infliximab treatment. A single infusion of infliximab significantly reduced the number of PBMC secreting TNF-alpha within 24 h. A rise in TNF-alpha production was associated with clinical deterioration. Infliximab treatment induced a significant increase in the number of cells secreting IFN-gamma and expressing IL-12Rbeta1. A favorable clinical response to infliximab was associated with a persistent reduction in TNF-alpha secretion, but did not correlate with IFN-gamma production. Our findings indicate that TNF-alpha plays a pivotal role in BD, and that anti-TNF-alpha therapy both reduces TNF-alpha production and modulates the functional activity of type 1 cells.