SUMMARYWehaveanalysed the role oflCAM-l and LFA-1 dtiring development of autoimmune sialadenitis in MRL/lpr mice by direct analysis of RNA obtained from the salivary gland tissues, and the therapeutic effects with antibody administration on adoptive transfer system into SCID mice. The expression of cell adhesion molecules was assessed by using reverse transcriptase polymerase chain reaction (RT-PCR) and Southern blot analysis, and immunohistochemical analysis. Up-regulated expression of lCAM-1 mRNA was observed before the onset of inflammatory lesions in the salivary glands at 1 month and 2 motiths old, and thereafter LFA-t mRNA was expressed within the typical inflammatory lesions, resembling human Sjogren's syndrome in MRL/lpr tnice. Immunohistochemically. ICAM-I was localized exclusively in the endotheliai cells of varying sized blood vessels before the onset of disease, and LFA-1 expressing inflammatory ceils were found within these lesions. When the therapeutic effects in vivo were examined, antibodies to ICAM-1 in combination with anti-LFA-1 prevented adoptive transfer of Sjogren's syndrotne in MRL/lpr mice into SCID mice, while no significant efl'ect was found when treated with either antibody. These findings indicate that in Sjogren's syndrotne-like autoimmune lesions in MRL/lpr mice the ICAM-l/LFA-1 pathway may play a crucial role in the initiation and subsequent progression of T cell-mediated autoimmunity in the salivary and lacrimal glands of M RL/lpr mice.