Abstract Familial Mediterranean fever (FMF) is a recessively inherited inflammatory disorder, characterised by recurrent attacks of fever and serositis. Since nitric oxide (NO) is an important mediator of inflammation, the production of NO (assessed as the accumulation of nitrate and nitrite and measured by capillary electrophoresis) in blood plasma of FMF patients during acute attacks (active) and attack-free periods (inactive) of the disease has been determined and compared with NO levels found in healthy volunteers (control group C). Thirty-six FMF patients were involved in a placebo-controlled double-blind study (group A received the drug, group B the placebo) of the effects of Immuno-Guard, a novel herbal preparation which relieves the severity and longevity of FMF attacks on NO blood levels. Thirty-two FMF patients (group D) being permanently treated with colchicine were also examined with respect to their NO blood level. No significant differences were found between the NO levels in blood of inactive FMF patients and those of control group C, or between inactive colchicine-treated group D patients and inactive patients of groups A and B, a finding which is atypical for chronic inflammatory disorders. Significantly lower plasma NO levels were found in active FMF patients in groups A and B compared with inactive patients in those groups ( p=0.031 and 0.036, respectively) and with patients of group D and the control group C ( p=0.0235 and 0.0453, respectively). The decrease of NO in blood of FMF patients may trigger the generation of fever by initiating the production of pro-inflammatory IL-6. Plasma NO levels in inactive FMF patients were significantly increased during attack-free periods following treatment with Immuno-Guard. The preparation has a normalising effect both on NO and IL-6 blood levels in FMF patients during attacks, demonstrating a relationship between the beneficial effect of Immuno-Guard in reducing the severity of inflammatory attacks in FMF patients and the increase in NO blood levels.