The results of a recent investigation, in which an antiserum specifically directed against Hodgkin (H) and Sternberg-Reed (SR) cells was prepared, indicated the existence of a granulocytic cell-specific antigen on H and SR cells. In the present study, a large series of biopsies from patients with Hodgkin's disease were subjected to immunostaining with monoclonal mouse antibodies raised against acute myelomonocytic leukemia (AMML) cells. Among seven hybrids that secreted antibodies showing reactivity to AMML cells but not to Daudi cells, there were three (TU5, TU6 and TU9) whose antibodies selectively stained formalin resistant antigens in cells of granulopoiesis. The strongest staining was found in the more mature cells; only a few promyelocytes stained very faintly with TU9, H and SR cells showed distinct staining for TU9 in 57 (76%) of the 75 tested cases of Hodgkin's disease, whereas TU5 and TU6-reactive H and SR cells were found in only 35 cases (47%). All cases of the nodular sclerosis type and almost all cases of the mixed cellularity type contained TU9-reactive H and SR cells, although the percentage varied from case to case. TU9-reactive H and SR cells were demonstrated in nine of 12 cases of the lymphocyte depletion type and in eight of 21 cases of the lymphocyte predominance type. The presence of granulocytic cell-specific antigens in H and SR cells in most of the cases of Hodgkin's disease suggest that (1) H and SR cells (including the lacunar cell variant) are not heterogeneous, but rather homogeneous in origin and nature, at least in a majority of cases, and (2) H and SR cells are more closely related to cells of the granulocytic cell lineage than to any other type of cell of the hemato-lymphoid system.