In autoimmune thyroid disease (AITD), the proportion of CD4 lymphocytes is lower in the thyroid than in the peripheral blood. We examined both Fas and Fas ligand (FasL) expression in lymphocyte subsets and nonlymphoid mononuclear cells including monocytes, macrophages, and dendritic cells (M/DCs) in both peripheral blood and thyroid specimens from 11 patients with Graves' disease and 1 with Hashimoto's disease by three-color flow cytometry. Proportions and intensities of Fas expression were increased in CD4 single-positive (SP) (CD4(+) CD8(-)), CD8 SP (CD8(+) CD4(-) ), and CD4(+) CD8(+) double-positive (DP) lymphocytes in AITD thyroids compared to those in blood, and were much higher in CD4(+) (CD4 SP and DP) lymphocytes than in CD8 SP lymphocytes in the thyroid. In the blood, most M/DCs expressed only CD4, but approximately 60% of M/DCs expressed both CD4 and CD8 in AITD thyroid. The proportion of DP M/DCs expressing FasL was higher in thyroid than in blood; proportion and intensity of FasL expression were much higher in DP M/DCs than in CD4 SP and CD8 SP M/DCs in the thyroid. These data indicate that increased Fas expression in intrathyroidal CD4(+) T lymphocytes may be the cause of CD4 lymphocyte reduction in AITD thyroid, and that intrathyroid DP M/DCs with high FasL expression may be related to the reduction in AITD.