Reed-Sternberg cells, the neoplastic cells of Hodgkin's disease, express all membrane molecules required to function as antigen-presenting cells (APCs), such as major histocompatibility complex (MHC) class II antigens and the recently characterized B7 proteins, which are of critical importance for APC to adequately stimulate CD4+ T cells. As APC do, Reed-Sternberg cells also express the adhesion molecules ICAM-1 (CD54) and LFA-3 (CD58), via which T cells are able to adhere to the cell. MHC antigens, B7 proteins as well as the adhesion molecules are expressed by Reed-Sternberg cells in virtually all cases of Hodgkin's disease, irrespective of the subtype. In vitro studies have shown that Hodgkin's disease-derived cell lines are potent stimulators of mixed lymphocyte cultures and that the MHC antigens, B7 proteins and the adhesion molecules, expressed by Hodgkin's disease-derived cell lines, are essential for such a function. Taken together, these data strongly suggest that Reed-Sternberg cells function as APC in vivo, and that the APC function of the cell is a major common denominator of Hodgkin's disease. The APC function of Reed-Sternberg cells does not support the hypothesis that they derive from dendritic cells, since activated B and T cells may also exert an APC function. Analysis of the antigens that are potentially expressed by Reed-Sternberg cells may greatly advance our knowledge on the pathogenesis of Hodgkin's disease and may allow the development of immunotherapy as an alternative treatment method.