To analyze potential associations of Glu-Asp298 polymorphism in exon 7 and 4 a/b polymorphism in intron 4 of the endothelial nitric oxide synthase (eNOS) gene with susceptibility for Behçet's disease (BD).Seventy-three consecutive Italian patients who satisfied the International Study Group criteria for BD and 135 healthy blood donor controls from the same geographic area were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for eNOS polymorphisms in exon 7 and in intron 4.The distribution of the Glu-Asp298 genotype differed significantly between BD patients and controls (p(corr) = 0.00009). Allele Asp298 was significantly more frequent in BD patients than in controls (p(corr) = 0.0006, OR 2.1, 95% CI 1.5-3.3). The distribution of 4 a/b genotype was similar in patients and controls.Our findings show that Glu-Asp298 polymorphism of eNOS gene is associated with BD susceptibility.