In this study we aimed to investigate IVS3 +17T/C single nucleotide polymorphism (SNP) of CD28 gene, +49A/G and -318C/T SNPs of CTLA-4 gene in patients with Behcet's disease (BD) and their potential association to the main clinical features of the disease. These polymorphisms were investigated in a Turkish population of 123 patients with BD and 179 healthy controls, by using PCR-RFLP technique. HLA-B*51 genotype was also studied in both groups by using PCR-SSP. The frequency of IVS3 +17TC genotype of the CD28 gene was significantly increased in BD patients compared to controls (43.6% vs. 31.2%, OR = 1.663, 95% CI = 1.033-2.679, P = 0.039). CTLA-4 +49GG genotype frequency was found to be significantly lower in patients with BD than those of healthy controls (4% vs. 10.6%, OR = 0.357, 95% CI = 0.130-0.983, P = 0.05). Genotype and allele frequencies of the CTLA-4-318C/T polymorphism between the BD and healthy control groups were not significantly different (12.2% vs. 10.6%, OR = 1.170, 95% CI = 0.570-2.402, P = 0.713). There were no associations between the studied polymorphisms and the main clinical features of BD. The frequencies of HLA-B*51 were 60.3% and 30.7% in BD and control groups, respectively (OR = 3.429, 95% CI = 2.115-5.559, P = 0.0001). Association between HLA-B*51 and each studied polymorphism did not reach to significant levels (OR = 0.479, 95% CI = 0.228-1.004, P = 0.064 for CD28 IVS3 +17TT genotype; OR = 2.180, 95% CI = 1.025-4.639, P = 0.061 for TC genotype; OR = 1.570, 95% CI = 0.870-2.836, P = 0.146 for C allele). These results may suggest that CD28 IVS3 +17TC genotype may be a risk factor for the development of BD, on the contrary CTLA-4 +49GG genotype may be protective in the studied Turkish population.