Previous immunohistochemical studies of the thyroid gland in Graves' disease (GD) have demonstrated that (i) lymphoid cells infiltrating the interstitium of the gland predominantly express the CD4+ (T-helper) phenotype; (ii) lymphoid cells infiltrating the epithelial compartment express predominantly the CD8+ antigen; and (iii) thyroid epithelial cells (thyrocytes) express class II histocompatibility antigens, possibly in response to endogenous production of interferon-gamma (IFN-gamma) by the infiltrating lymphocytes. In the present study the infiltrating lymphoid cells and thyrocytes in GD were further characterized by immunocytochemistry. Scattered infiltrating interstitial lymphocytes stained positively with antibodies directed against IFN-gamma and the receptor for interleukin 2. These lymphocytes were most prominent around the periphery of lymphoid nodules. The interstitial lymphocytes predominantly expressed the CD4+ 2H4+ phenotype rather than the complementary CD4+ 4B4+ phenotype, suggesting the presence of the suppressor-inducer rather than helper-inducer T cell subset. The infiltrating lymphocytes were associated with thyrocytes expressing HLA-DR antigens, as previously reported, and also HLA-DQ antigens, but to a lesser extent. The presence of HLA-DQ may also suggest the possibility of an induced suppressor response. The intraepithelial CD8+ cells did not stain with antibodies to CD3, 2H4, 4B4, or Leu 7 and their identity remains unknown.