Genetic factors that predispose individuals to Behcet's disease (BD) are considered to play an important role in the development of the disease. The serum level of tumor necrosis factor (TNF) is elevated in patients with BD, and a dramatic response to anti-TNF-alpha antibody treatment further supports the role of TNF in BD. We investigated the distribution of TNF-alpha promoter -1031T/C and -308G/A polymorphisms in 53 BD patients of Iranian Azeri Turks and 79 matched healthy controls, via the PCR-RFLP technique. The frequency of the TNF-alpha -1031C allele was significantly higher in Behcet's patients than in healthy controls (p < 0.0001, OR = 3.08; 95% CI = 1.73-5.47), whereas the frequency of the TNF-alpha -308A allele was similar in the two compared groups. The frequency of CG haplotype was significantly higher (p < 0.0001, OR = 3.42; 95% CI = 1.89-6.18), and that of the TA haplotype was significantly lower in BD patients than in healthy controls. These results suggest that TNF-alpha is a susceptibility gene for BD in patients from Iranian Azeri Turk ethnic group.