Multiple myeloma represents a B cell malignancy characterized by a monoclonal proliferation of plasma cells. A striking feature of the disease is the tendency of the malignant plasma cells to affect mainly the bone marrow environment and to invade the peripheral blood only in the terminal stage. The growth of myeloma plasma cells is believed to be regulated by a functional interplay between the tumor cells and the bone marrow stroma, involving the action of various cytokines. This growth control is most probably mediated by close cellular contact of the myeloma cells and marrow stromal components. Therefore it can be assumed that myeloma plasma cells possess the ability to interact with the bone marrow stroma. Until now the adhesive mechanisms that may underlie this interaction, remain undetermined. We investigated the expression of several adhesion molecules on bone marrow plasma cells in myeloma patients and normal controls. Normal as well as malignant plasma cells were found to be strongly positive for the intercellular adhesion molecule ICAM-1, the fibronectin receptor VLA-4 and the lymphocyte homing receptor CD44. In addition, a much weaker expression of the second fibronectin receptor VLA-5, the laminin receptor VLA-6 and the vitronectin receptor CD51 was demonstrated. In contrast to normal plasma cells, myeloma cells can also express the neural cell adhesion molecule N-CAM. In this report we discuss the possible role of adhesion molecules in the pathogenesis and clinical evolution of multiple myeloma.