Behcet's disease (BD) is a relapsing immuno-inflammatory vasculitis of unknown etiology characterized by endothelial dysfunction. Articular symptoms and signs are present in about 75% of cases and characterized by seronegative arthritis and nonspecific synovitis. We demonstrated that both serum and erythrocyte nitric oxide (NO center dot) levels, the most abundant free radical in the body, were elevated in BD and associated with disease activity. This study further investigated NO center dot levels in the synovial fluid and serum from patients with active and inactive BD. A total of 23 BD patients with articular involvement ( 14 men and 9 women) satisfying International Study Group criteria and 15 age- and sex-matched healthy control subjects ( 9 men and 6 women) undergoing elective arthroscopy were included in this case-control investigation. The synovial fluid and serum were obtained from BD patients and controls. Clinical and laboratory findings including neutrophil count and erythrocyte sedimentation rate (ESR) were used to classify BD patients as active (n = 11) or inactive (n = 12). Synovial as well as serum NO center dot levels were compared between the groups and correlation analysis was performed. Acute phase reactant levels were significantly higher ( for each, p< 0.01) in BD patients than control subjects in the active period. The mean synovial NO center dot level in active Behcet's patients ( mean +/- SD 76.61 +/- 11.95 mu mol/l) was significantly higher than in inactive patients (46.16 +/- 8.89 mu mol/l, p< 0.001) and healthy control subjects (39.60 +/- 8.03 mu mol/l, p< 0.001). The difference between inactive patients and controls was not significant ( p> 0.05). Active BD patients had significantly higher serum NO center dot levels ( 38.84 +/- 9.15 mu mol/l) than inactive patients (30.91 +/- 5.88 mu mol/ l, p = 0.018) and control subjects (28.86 +/- 5.91 mu mol/ l, p=0.002). In addition, synovial NO center dot levels were positively correlated with serum levels (r(2) = 0.621, p< 0.001). Increased synovial NO center dot levels in active BD patients probably reflect a nonspecific inflammatory process of the synovium and, therefore, arthralgia and arthritis as a common finding of BD.