Plasma cells isolated from bone marrow (BM) aspirates of 15 patients with active multiple myeloma (MM) were cultured and analysed for in vitro proliferative response and Ig-synthesis upon stimulation with interleukin-3 (IL-3), interleukin-4 (IL-4) and interleukin-6 (IL-6). The proliferative response, determined as Ki-67 positivity in concentrated plasma cells, was increased by IL-6 (Stimulation Index, SI = 1.77 +/- 0.21 (M +/- SEM] but not by IL-3 or IL-4. This proliferation could be blocked by anti-IL-6. In vitro Ig-synthesis was stimulated by IL-4 (SI = 1.62 +/- 0.12 (M +/- SEM) P less than 0.05) but not by IL-6 or IL-3. This effect was not antagonized by anti-IL-6. An inverse correlation was found in this group of patients between the IL-6 induced stimulation of plasma cell proliferative activity and the IL-4 induced increase of Ig-synthesis (P = 0.027). These data indicate in MM that Ig-synthesis and the in vitro proliferative activity may be stimulated by different haematopoietic growth factors, which may reflect the involvement of different responding cells.