Patients with chronic graft-versus-host disease (cGVHD) occasionally suffer from symptoms of xerostomia and xerophthalmia, which are also features of Sjógren's syndrome (SS). To identify differences in the glandular involvement between cGVHD and SS, we measured the proportions of infiltrating lymphocyte subsets and the expression of HLA-DR antigen and cell adhesion molecules in labial salivary glands (LSG). In cGVHD, more than 90% of the infiltrating lymphocytes were T cells with a slight predominance of CD8+ over CD4+ cells. In SS, CD4+ cells were predominant, and B cells accounted for 10-30% of the infiltrating lymphocytes. Ductal epithelial cell associated with lymphocytic infiltration expressed HLA-DR antigen in both cGVHD and SS. In SS alone, HLA-DR antigen expression also occurred without associated lymphocytic infiltration. The expression of adhesion molecules on ductal epithelial cells, especially vascular cell adhesion molecule 1, was more intense in SS than in cGVHD, while that on endothelial cell was similar in cGVHD and SS. These data suggest that the pathogenesis of glandular involvement of cGVHD is different from that of SS.