Nitric oxide (NO) is a molecule that plays a key role in many physiologic and pathologic processes. It is produced in vivo from the aminoacid l-arginine by a family of nitric oxide synthases (NOS). Endothelial NOS (eNOS) is a constitutively expressed isoform of NOS. The eNOS gene entails several polymorphisms, of which certain were investigated in Behçet's disease (BD). We sought to establish the association of eNOS gene Glu298Asp polymorphism in exon 7 with susceptibility to BD. In this study, 135 Tunisian patients with BD and 157 healthy blood donor controls from the same geographic area were genotyped by polymerase chain reaction technique for eNOS polymorphism in exon 7. Our results showed that the distribution of the Glu298Asp genotype differed between BD patients and controls but did not reach statistical significance (p = 0.06). Allele Asp298 was significantly more frequent in healthy controls than in BD patients (p = 0.037, chi(2) = 4.33, OR = 1.01, 95% CI = 1.41-1.99). A significant difference was found (p = 0.004, OR = 1.26, 95% CI = 2.13-3.62) between BD patients with skin lesions and patients without this manifestation. Our findings suggest that Glu298Asp polymorphism of eNOS gene is associated with BD susceptibility as well as skin lesions.