Sjögren's syndrome [SS] is typified by infiltration of mononuclear cells [MNC] into the salivary and lacrimal glands, although the biological role of these infiltrating cells remains unclear. We report here that E-cadherin, which mediates cell–cell adhesion and regulates differentiation, proliferation, and apoptosis of epithelial cells, is expressed ectopically by MNC in the salivary glands in the NOD mouse model of SS. Flow cytometric analysis of CD45+cells from NOD submandibular glands revealed that over 90% express E-cadherin. More detailed phenotypic analyses demonstrated that E-cadherin expression is high (>90%) among mature T cells (CD3+), B cells (CD19+), NK cells (DX5+), and monocyte/macrophages (CD11b+) within the infiltrates. Expression of other surface antigens, such as CD90 and CD117, above expected values suggests the presence of immature leukocytes, possibly of the T cell lineage, within the foci. We also present evidence that E-cadherin-expressing T cells in the glands do not exhibit normal proliferative responses to immobilized anti-CD3 antibody. While infiltrating MNC are not likely to be the direct cause of salivary hypofunction, the expression of E-cadherin by these cells may have implications for the progression of disease.