BACKGROUND: Familial Mediterranean fever (FMF) is a genetically linked disorder common amongst races of the Eastern Mediterranean region. Typical symptoms include episodic pain syndrome extending throughout the chest or abdomen associated with histopathological signs of amyloidosis of the kidney. AIM: To investigate possible connections between the aseptic inflammation that occurs during pain crises and cell membrane structural and functional integrity in patients with FMF. METHODS: Oxidative stress parameters in 42 patients in remission and during a pain crisis were compared with 21 normal subjects. RESULTS: The patient group had significantly greater concentrations of chemiluminescent and thiobarbituric acid-reactive substances in the blood plasma and lower concentrations of alpha-tocopherol than the control group while in remission; these changes were exacerbated during pain crises. Analyses of the phospholipid composition of erythrocyte membranes showed significant increases in amounts of acidic phospholipids (phosphatidic acid, monophosphatidylinositol and cardiolipin) and lysophosphatidylcholine compared with healthy subjects. CONCLUSIONS: The pattern of differences in membrane phospholipid composition was consistent with increased oxidative stress in patients with FMF.