AIMS: To investigate the possibility of an immune response to retroviral antigens or of detecting retrovirus in Sjögren's syndrome. METHODS: Retroviruses were sought in labial salivary glands and peripheral blood mononuclear cells from patients with Sjögren's syndrome by immunoblotting assay, immunohistochemical assay, polymerase chain reaction (PCR), reverse transcriptase (RT) activity assay, and transmission electron microscopy. RESULTS: Sera from five of 15 patients with Sjögren's syndrome (33%) reacted against p24 group specific antigen (gag) of human immunodeficiency virus (HIV). Labial salivary gland biopsy specimens from seven of the 15 patients with Sjögren's syndrome (47%) contained an epithelial cytoplasmic protein reactive with a monoclonal antibody to p24 of HIV. PCR was performed to detect HIV and human T lymphotropic virus type I (HTLV-I) genes from salivary gland tissues and peripheral blood mononuclear cells from patients with Sjögren's syndrome. Mn2+ dependent, Mg2+ independent RT activity was detected in the salivary gland tissues in three of 10 patients. A-type-like retroviral particles were observed in epithelial cells of salivary glands by transmission electron microscopy. Target genes for HIV and HTLV-I were not found in any of the salivary gland tissues or peripheral blood mononuclear cells from Sjögren's syndrome patients. CONCLUSIONS: The data suggest the presence of an unknown retrovirus similar to HIV in the salivary gland which might be involved in the pathogenesis of a subpopulation in Sjögren's syndrome.