Long-term bone marrow cultured stromal cells (LTBMC) produce IL-6 after contact with tumour cells from multiple myeloma patients. We found that LTBMC could substitute for exogenous IL-6 in the stimulation of bone marrow plasma cells from myeloma patients with active disease in short-term cultures. In addition, tumour cells of some patients with inactive disease, which were unresponsive to exogenous IL-6, were induced to IL-6-dependent growth after LTBMC co-culture. To study the role of LTBMC in myeloma tumour growth in vitro, plasma cell lines UM-2 and UM-3 were selected. UM-2 and UM-3 grew in contact with LTBMC and proliferation was blocked by antibodies against IL-6, IL-6 receptor (IL-6R, gp80, CD126) or the common signal transducing unit, gp130 (CD130). Culture with IL-6 alone or combined with GM-CSF resulted in cell death via apoptosis. The combination of IL-6 with soluble gp80, however, maintained in vitro proliferation of UM-2 and UM-3 cells. These data imply that LTBMC regulate myeloma growth in vitro via production of IL-6, possibly via induction of a functional IL-6 receptor on the tumour cells.