Sjögren's syndrome (SS) is a unique disease which develops a high incidence of lymphoproliferative disorder such as monoclonal gammopathy or malignant lymphoma. In order to elucidate the mechanism of the progression from polyclonal to monoclonal lymphoproliferation in SS patient, we analyzed the monoclonal nature and the expression of bcl-2 protein in the salivary glands. Formalin-fixed, paraffin-embedded salivary gland (labial salivary glands, 45; parotid glands, 6; submaxillary glands, 1) tissues or lung tissues (interstitial pneumonia in 2 patients with SS) were serially sectioned and evaluated using the standard avidin-biotin-peroxidase (ABC) technique. Murine monoclonal primary antibodies obtained from Dakopatts to B-cells (L26; CD20) and T-cell markers (UCHL1; CD45RO) and bcl-2 protein were employed. The bcl-2-positive areas were stained with T and B cell markers in serially sectioned specimens. Lymphocytes forming the LEL were mostly composed of CD20-positive B-cells and these cells expressed bcl-2 protein. In the lip biopsy specimens, 36 of 45 patients showed small areas of bcl-2 expression in periductal lymphocytes. The expression of bcl-2 protein in the cells plays a crucial role in the cells escaping apoptotic cell death, living long and resulting in autoantibody production, and obtaining the increased risk of monoclonal proliferation of the cells. These findings provide further evidence for understanding the mechanism of monoclonal transformation from polyclonal lymphoproliferation in autoimmune reaction.