Research into the role of Epstein-Barr virus (EBV) in the pathogenesis of SS has been a focus of interest for the past decade. The use of EBV as a probe for cellular and humoral immune responses has contributed to our current understanding of SS. However, it is still difficult to assign a role to EBV in the pathogenesis of SS. We have already demonstrated a) increased excretion of EBV in the saliva of SS, increased levels of EBV DNA in salivary gland biopsies of SS patients and spontaneous and massive production of transforming EBV in B cell lines established from SS patients. These data suggest that the reactivation of EBV might be deeply involved in disease perpetuation, polyclonal B cell activation and B cell malignancy in SS, even if it is not the primary cause. Recently, we examined the nucleotide sequence of the U2 region in EBV obtained from SS patients. The U2 region contains genes encoding EBNA-2, which plays an important role in B cell transformation and activation. In addition, studies on the breakdown of self-tolerance, and intriguing evidence supporting a potential role for infectious agents such as EBV and retroviruses also offer novel views of inflammation of salivary gland. This review will discuss recent advances in these subjects.