The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) plays an important role on the course of disease in familial Mediterranean fever (FMF). TNF-alpha gene promoter polymorphism may be a marker of susceptibility and severity of FMF. The aim of this study is to evaluate both TNF-alpha/238 and TNF-alpha/308 genotypes and allelic distribution in patients with FMF. Forty-one FMF patients and 43 healthy volunteers were included in the study. Genomic DNA was extracted from EDTA-preserved whole blood of whole series of patients and controls. Polymorphism of TNF-alpha promoter at positions -238 and -308 were detected by using amplification refractory mutation system polymerase chain reaction. TNF-alpha/238 and TNF-alpha/308 genotype distributions and allele frequencies of FMF patients and healthy volunteers were found to be similar. Moreover, there was no association between TNF-alpha/238 and TNF-alpha/308 genotypes and the frequency of acute attacks in FMF. TNF-alpha/238 and TNF-alpha/308 promoter polymorphisms do not seem to be major genetic risk factors for susceptibility to FMF and severity of the disease.