The biological attributes and cellular origin of the malignant cells in Hodgkin's disease have been subject to numerous investigations both on fresh biopsy material and from long-term in vitro cultures of cells derived from Hodgkin's disease lesions. Studies on fresh biopsy material have led to suggestions that Hodgkin's cells are derived from T-lymphocytes, B-lymphocytes, or monocytes/macrophages. However, all these studies are hampered by the low amounts of Reed-Sternberg cells in the neoplastic lesions as well as some technical difficulties. It has consequently been desirable to establish long-term cell cultures of the malignant Hodgkin's cells, and the technical problems as well as the experimental outcome of these studies are reviewed. Among the technical, the potential and limitations in the use of monoclonal antibodies are described in particular. A number of cell lines from Hodgkin's disease lesions have been described, but a critical appraisal of these studies reveal that most of the published cell lines can be dismissed as being non-representative for Hodgkin's and ReedSternberg cells; most of the cell lines are thus EBV-transformed lymphocytes and in some cases even nonhuman cell lines. Two cell lines (L428 and SU/RH-HD-1), however, seem to be derived from the malignant cell population in Hodgkin's disease. The phenotypic analyses of these lines-and in particular the SU/RH-HD-1 line—strongly indicate that cells have monocyte/macrophage attributes, and it is concluded that Hodgkin's disease is a neoplasm of cells in the monocyte/macrophage lineage.