Employing a series of monoclonal antibodies directed against T cell subsets and the ABC (avidin-biotin complex) method as the immunoperoxidase technique, we studied the distribution of T cell subsets in frozen tissue sections of tonsils in 8 cases with various tonsillar lesions. Anti-Leu 1 and anti-Leu 4 antibodies, which react with all peripheral T cells, stained a majority of interfollicular cells and mononuclear cells in the lymphoepithelial symbiosis (LES). Approximately 80% of Leu 1+ and Leu 4+ cells were reactive with anti-Leu 3a antibody, which defines the helper/inducer T cell subset. Small lymphocytes in the mantle zone of the tonsillar follicle had IgD and IgM on their surface, whereas the cells in the germinal center showed membrane and/or cytoplasmic staining with anti-IgM serum. In addition, Leu 3a+ cells were found in the germinal center, especially on the capsular side showing a linear distribution. On the other hand, anti-Leu 2a antibody, which defines the suppressor/cytotoxic T cell subset, stained only a minority of lymphocytes in the interfollicular area and in the LES. Leu 2a+ cells were rarely found in the germinal centers. Anti-HLA-DR-positive cells were found with two types of staining pattern, i.e., with membrane staining found in the small lymphocytes in the mantle zone and the germinal center and with membrane and/or cytoplasmic staining found in large cells with dendritic processes in the germinal center, in the LES, and in the interfollicular areas. These findings demonstrate the presence of intimate cellular interactions in T cells, B cells, and macrophages in the tonsil, and indicate that immunohistological study of the tonsil may provide new insights into the pathogenesis of tonsillar lesions.