Tumor necrosis factor alpha (TNF-alpha) is believed to play a significant role in disease pathogenesis of Behcet's disease (BD). High serum levels of TNF-alpha were repeatedly reported in patients with active BD and anti-TNF agents are effective in its treatment. The pathophysiology of TNF-alpha in BD is still unknown and conflicting results regarding TNF-alpha overproduction by peripheral blood monocytes (PBM) from patients with BD were reported. The aim of the study is to compare stimulated production of TNF-alpha by PBM of BD patients with that of healthy volunteers (HV) and to examine correlations between the ability of PBM to produce TNF-alpha and organ/system involvement in patients with BD. Eighteen patients with BD (mean age 38.4+/-12.4 years, 12 males) gave informed consent and completed the European BD Current Activity Form. The PBM were separated and treated with lipopolysaccharide (LPS) overnight. TNF-alpha levels in the supernatants were assayed by ELISA and values were expressed in terms of cell protein contents. The control group included 15 HV (mean age 34.2+/-9.9 years, seven males). The mean production of TNF-alpha/cell protein (ng/mg) and in-group dispersion were similar in both groups (p=0.98). In the subgroup analysis, TNF-alpha production by PBM in BD patients who reported "bad" or "very bad" global well-being over the last month (n=4) was higher compared to other patients with better self-rating (p=0.03). PBM of BD patients in the present study did not overproduce TNF-alpha upon stimulation with LPS. However, BD patients with a higher TNF-alpha-producing capacity had worse sense of well-being.