Cell lines derived from Hodgkin's disease may provide a clue to the nature of Sternberg-Reed cells. In the current study, the establishment of an Epstein-Barr-virus-negative lymphoblastoid cell line, derived from the pleural fluid of a patient with the nodular sclerosis type of Hodgkin's disease, is described. The morphologic and immunologic cell marker findings indicate that this cell line is derived from Sternberg-Reed cells. The immunologic findings and a chromosomal analysis are in agreement with a B-lymphocyte origin of these cultured cells. Extrapolation of the results to Hodgkin's disease in vivo would indicate that Hodgkin's disease, like most non-Hodgkin's lymphomas, is the result of B-cell proliferation.