There is growing evidence for a B-cell lineage of lymphocyte-predominant Hodgkin's disease (1). To support this assumption, in situ hybridization techniques were used to detect immunoglobulin light-chain mRNA in 44 formalin-fixed specimens of Hodgkin's lymphoma (22 of lymphocyte-predominant Hodgkin's disease; 22 of mixed-cellularity Hodgkin's disease). In addition, immunoglobulin light chains were evaluated by polyclonal antisera. All specimens had been unequivocally diagnosed histologically by the referees of the German Hodgkin Trial and been immunophenotyped by monoclonal antibodies against CD15, CD20, CD30, and CD45. Light-chain mRNA coding either for kappa or for lambda could be detected by an enhanced in situ hybridization protocol using microwave heating in the lymphocytic and histiocytic cells of 14 (64%) of 22 specimens of lymphocyte-predominant Hodgkin's disease tested. None of the specimens, however, belonging to one of the classic subtypes of Hodgkin's disease (mixed-cellularity Hodgkin's disease) showed positivity for mRNA in the giant tumor cells. Our results support the idea that lymphocyte-predominant Hodgkin's disease represents a B-cell malignancy that is a entity separate from classic Hodgkin's disease. Diverging results of former studies in assessing light-chain mRNA in lymphocytic and histiocytic cells probably reflect problems with the detection threshold, i.e., the sensitivity of the techniques applied.