In order to further define the pathobiologic changes that occur in Hashimoto's thyroiditis (HT) and Graves' disease (GD), 47 cases of these conditions and six of nodular thyroid hyperplasia were studied. Antibodies to cytokeratin, vimentin, LN-2 (a B-lymphocyte marker), UCHL-1 (a T-lymphocyte marker), and HLA-DR, and biotinylated Helix pomatia (Roman snail) lectin, were applied to paraffin sections using the avidin-biotin-peroxidase complex method. Cytokeratin was not expressed in resting epithelium or nodular hyperplasia, but was strongly displayed by injured (HT) or diffusely hyperplastic (GD) glandular tissue. Vimentin was present throughout the cytoplasm of proliferating thyrocytes but was limited to basal portions of resting cells and those of nodular hyperplasia. HLA-DR was observed in injured and hyperplastic thyroid tissue, as was N-acetyl-alpha-D-galactosamine, the target of H pomatia lectin. UCHL-1-labeled infiltrating lymphocytes were observed in both HT and GD, in areas with minimal epithelial changes, while LN-2 was observed only in association with well-formed lymphoid follicles. These findings suggest that T cells are implicated in the mechanism of both conditions, but that inflammation is not the initiating event for HT and GD; and that a "switch" in intermediate filament synthesis accompanies HLA-DR and N-acetyl-alpha-D-galactosamine expression by thyroid epithelium. Since current theories implicate intermediate filaments as intracellular mediators, we hypothesize that certain cytokeratins may be associated with gene activity governing the expression of class II histocompatibility antigens and other membrane glycoproteins in HT and GD.