The etiology of Behçet's disease is unclear, but viral infection is thought to be one etiologic factor. The aims of this study were to detect herpes simplex virus (HSV) DNA in the saliva of patients with Behçet's disease and of healthy persons, to determine whether the presence of HSV in saliva is associated with the presence of intraoral ulcer, and to investigate the relationship between HSV and Behçet's disease. The polymerase chain reaction (PCR) was used to detect HSV DNA sequences in DNA extracted from the saliva of patients with Behçet's disease and of healthy control subjects. Of 66 patients with Behçet's disease diagnosed clinically, 19 were diagnosed as complete type, 29 as incomplete type and 18 as suspected type. Of 66 DNA preparations from the saliva of the patients, 26 (39.4%) showed the 289-bp band. This contrasts with 12 of 87 preparations (13.8%) from healthy controls (P < 0.01). There were no significant differences among the three patient groups. All the 289-bp bands analyzed by restriction endonuclease digestion yielded the expected 158-bp and 131-bp fragments when digested with PstI.HSV DNA was detected in 12 of 33 Behçet's disease patients (36.4%) with oral ulceration and 14 of 33 patients (42.4%) without oral ulceration at the time of testing. There was no statistically significant correlation in the PCR results between the two groups.