The lymphocytes surrounding Reed-Sternberg cells may play an important role in the pathogenesis of Hodgkin's disease. In this study, T cells in different subtypes of Hodgkin's disease were analyzed in situ by an immunoperoxidase method employing a panel of antibodies, including several paraffin tissue-reactive monoclonal antibodies. The T cells in Hodgkin's disease-involved tissues were found to be activated CD4-positive T cells that are UCHL1+ and CD45R-. This immunophenotype is compatible with an activated helper-inducer memory T cell population. The T cells in the nodular lymphocyte predominance subtype were found to have additional positivity for Leu 7, indicating a subpopulation of CD4+ T cells, normally confined to the light zone of germinal centers of secondary follicles.