The presence, marker pattern, and ultrastructure of antigen-presenting dendritic cells were studied in normal thyroid glands from 9 subjects (6 obtained at surgery; 3 at autopsy) and in the thyroid glands form 13 patients with Graves' hyperthyroidism, 10 patients with simple nontoxic goiter, and 1 patient with Hashimoto's disease (all obtained at surgery). The immunohistochemical characterization of the cells was carried out using the monoclonal antibodies OKIa (class II MHC determinants), RFD1 and L25. These latter monoclonal antibodies react strongly with active dendritic cells in T-cell areas of secondary lymphoid organs (the interdigitating cells in lymph nodes and spleen). Antigen-presenting dendritic cells were defined as cells with an eccentric reniform nucleus, long cytoplasmic protrusions, and strong membrane-bound class II MHC positivity combined with little or no cytoplasmic acid phosphatase activity. According to these criteria normal human thyroid tissue contained a few dendritic cells; they were localized outside the thyroid follicles. These dendritic cells in normal thyroid tissue lacked the marker molecules identified by the monoclonal antibodies RFD1 and L25. In fact, the majority of the dendritic cells were strongly positive for the C3bi receptor (identified by the monoclonal antibody FK 24), which indicates a more monocyte/macrophage character of the cell. In Hashimoto's goiter, Graves' disease, and sporadic nontoxic goiter (which we consider an autoimmune thyroid disease) the numbers of dendritic cells were higher compared to those in the normal gland, and these dendritic cells were clearly positive for RFD1 and L25. The cells were often seen in contact with a few intrathyroidal lymphocytes, forming small lymphoid cell clusters. They were also found in the T-cell zones of larger well organized intrathyroidal lymphoid structures (focal thyroiditis). On ultrastructural examination the dendritic cells in Graves' glands, Hashimoto's goiter, and sporadic nontoxic goiter were similar to the interdigitating cells present in secondary lymphoid organs. The data suggest active involvement of dendritic cells in the immune process in the thyroids of patients with autoimmune thyroid disease.