Follicular non-Hodgkin's lymphomas (NHL) generally present as disseminated diseases with infiltration of lymphoid organs, bone marrow (BM), as well as peripheral blood (PB). These lymphoma cells may recapitulate the behavior of normal germinal center (GC) B cells, some of which remain in follicles and others which have the capacity to migrate. Normal activated B cells and follicular lymphoma cells bind to GCs in vitro and this interaction is mediated by VLA-4 on the lymphoid cell and VCAM-1 on follicular dendritic cells. Since the disseminated nature of follicular NHLs may be related to the ability of PB and BM cells to recirculate through lymphoid tissues, we examined the adhesive characteristics of follicular lymphoma cells isolated from these site. Cells from 10 of 14 cases of follicular NHL involving PB or BM bound to normal GCs. Neoplastic GCs could similarly support the binding of PB or BM derived follicular NHL cells. This interaction was inhibited by monoclonal antibodies directed against VLA-4 and VCAM-1. These studies may provide insight into the clinical behavior of these diseases. More importantly the homing and adhesion of lymphoma cells is likely to be relevant to the use of PB and BM as a source of hematopoietic stem cells following high dose ablative therapy.