The present study was performed to elucidate the role of adhesion molecules in the pathogenesis of Graves' disease. Peripheral blood and intrathyroidal mononuclear-cells were obtained from 14 patients with Graves' disease. The expression of adhesion molecules and HLA-DR antigen on CD4+ cells and CD4+ cell subpopulations was analysed by the two- or three-colour immunofluorescence method. The expression of adhesion molecules including LFA-1alpha, LFA-1beta, CD2, VLA-4alpha and VLA-5alpha on CD4+ cells in the thyroid gland was markedly higher than that in peripheral blood. In peripheral blood CD4+ cell subsets, the CD4+CD45RO+ cell population had an enhanced expression of the adhesion molecules compared with the CD4+CD45RA+ cell population. However, there was no significant difference in the expression of adhesion molecules by CD4+ cell populations and subsets between Graves' disease and healthy subjects. The thyroid gland from Graves' disease contained a higher percentage of CD4+CD45RO+ cells and a lower percentage of CD4+CD45RA+ cells. In intrathyroidal CD4+ cell subsets, the CD4+CD45RO+ cell population had an increased expression of LFA-1 and CD2 compared with the CD4+CD45RA+ cell population, but there was no significant difference in VLA-4 and VLA-5 expression between the two cell subsets. Furthermore, the expression of LFA-1 and CD2 on the CD4+CD45RO+ cell population in the thyroid was significantly higher than that in matched peripheral blood. A similar finding was also observed for the CD4+CD45RA+ cell population. The thyroid gland had an increased percentage of CD4+HLA-DR+ cells compared with matched or healthy peripheral blood. However, there was no significant difference in the percentage of HLA-DR+ cells in the thyroid gland between CD4+CD45RO+ cell and CD4+CD45RA+ cell populations. These results suggest that increased expression of adhesion molecules on CD4+ cells may be responsible for the migration of these cells into thyroid glands and cellular interactions between these cells and thyroid epithelial cells.