Behçet's disease (BD) is a connective tissue disorder characterized by recurrent orogenital ulcer, uveitis, and skin lesions. Recurrent aphthous ulcer is associated with human cytomegalovirus (HCMV). To investigate the possible role of HCMV in BD, we measured the titers of IgG, IgM, and IgA anti-HCMV antibodies in 73 Korean patients with BD, 50 with scleroderma, 70 with systemic lupus erythematosus, and 50 from healthy controls by indirect immunofluorescent staining. The titer of IgG anti-HCMV antibody was significantly lower in patients with BD than in controls (geometric mean 3115.4 vs 9687.6, P = 0.0001 by Wilcoxon's rank sum test), as was the titer of IgA anti-HCMV antibody (geometric mean 1.9 vs 15.7, P = 0.0001, Wilcoxon's rank sum test). In conclusion, we found significantly lower antibody responses to HCMV in patients with BD.