Nodular lymphocyte predominance type of Hodgkin's disease can be distinguished from other subtypes of Hodgkin's disease on morphological and clinical grounds. Immunohistological studies on frozen tissue sections of seven cases of nodular lymphocyte predominance type of Hodgkin's disease (NLPHD) show differences in B cell, T cell, as well as dendritic cell population. NLPHD is confined to follicles which contain predominantly small lymphocytes, usually over 50% B cells and large numbers of B2+, anti-C3b+, anti-DRC+, and Ig- dendritic cells. The IgM+, IgD+, Leu8- B lymphocytes are of polyclonal origin. The T lymphocytes in these follicles are reactive with Leu7 in addition to T11, Leu1, T3, Leu3, and WT1. Leu7 is a monoclonal antibody reactive with natural killer cells, but also with a subpopulation of Leu3+ lymphocytes present in normal germinal centers. The population with this phenotype, not found in other types of Hodgkin's disease, appears to be greatly increased (up to 30%) in NLPHD. The so-called L&H type Sternberg-Reed (S-R) cells of NLPHD are transformed B cells, reactive with anti-B cell monoclonal antibodies which in some cases express detectable amounts of membrane and/or cytoplasmic immunoglobulin. Also, L&H type Sternberg-Reed cells in all cases stained for Ki-1 and Tac, and in three cases for LeuM1. Taken together, the findings indicate that NLPHD represents a proliferation of germinal center cells.