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PURPOSE: To determine whether Epstein-Barr virus (EBV) could be involved in the pathogenesis Sjogren's syndrome (SS). PATIENTS AND METHODS. In situ hybridization using the BamHI-W fragment of EBV DNA was performed using labial salivary gland biopsy sPecimens from 14 patients with SS (eight with Primary SS and six with secondary SS) and 39 control subjects. Furthermore, labial salivary gland biopsy specimens from 12 patients with SS (seven with primary SS and rive with secondary SS) and 24 control subjects were submitted to the polymerase chain reaction to detect EBV DNA. RESULTS: In situ hybridization detected EBV DNA in epithelial cells of labial salivary gland bioPsy specimens from four of eight (50%) patients with primary SS, zero of six patients with secOndary SS, and three of 39 (8%) control subjects. The difference between patients with primary SS and control subjects was statistically significant p, Sjogren's syndrome (SS) is characterized by the accumulation of lymphocytes, a type of immune cell, in the salivary and lacrimal (tear) glands, and the production of abnormal immune proteins called autoantibodies. Several lines of evidence suggest that infection with the Epstein-Barr virus (EBV) may be involved in the development of SS. However, the role of EBV infection in the development of SS remains unclear. The presence of EBV was assessed in the salivary glands of patients with SS using molecular biology methods. The DNA of EBV was detected by in situ hybridization in the epithelial cells located on the surface of the salivary glands from: four of eight patients (50 percent) with primary SS, or SS unrelated to other medical conditions; none of six patients (0 percent) with secondary SS, or SS associated with another medical problem; and three of 39 subjects (8 percent) without SS. Another molecular biology technique, the polymerase chain reaction, was used to detect EBV DNA in six of seven patients (86 percent) with primary SS; three of five patients (60 percent) with secondary SS; and seven of 24 subjects (29 percent) without SS. These results show that the genetic material of EBV can be detected with a greater frequency in patients with SS than subjects without SS. The epithelial cells of the salivary glands appeared to be the major site of infection by EBV. These findings suggest that EBV infection plays a role in the pathogenesis of SS. However, it remains unclear whether the virus causes deterioration of the salivary glands or whether infection occurs after injury of the gland. (Consumer Summary produced by Reliance Medical Information, Inc.)