We have analyzed the role of cell adhesion molecules during the development of autoimmune dacryodenitis in an NFS/sld mouse model for primary Sjögren's syndrome. The expression of cell adhesion molecules was assessed by RT-PCR and immunohistochemistry. We detected an up-regulation of local cell adhesion molecule genes (ICAM-1, LFA-1, CD44 and Mel-14) in the course of autoimmune lacrimal gland diseases. Immunohistochemically, ICAM-1 was localized exclusively in the endothelial cells of variously sized blood vessels before the onset of disease, and LFA-1, CD44 and Mel-14, expressing infiltrating cells, were found within these lesions. When the therapeutic effects of blocking cell adhesion molecules in vivo were examined, antibodies to ICAM-1 in combination with anti-LFA-1 prevented the development of autoimmune lacrimal gland diseases in NFS/sld mice. These data suggest that in Sjögren's syndrome-like autoimmune dacryoadenitis in NFS/sld mutant mice, the ICAM-1/LFA-1 pathway may play a crucial role in the development and subsequent progression of T-cell-mediated autoimmunity in the lacrimal glands.