Peripheral blood mononuclear cells (PBMC) from 14 patients with multiple myeloma (MM), 3 patients with benign monoclonal gammopathy, 3 patients with Waldenstrom's macroglobulinaemia (WM) and 2 patients with B-cell chronic lymphocytic leukemia (B-CLL) were cultured in vitro in the presence of IL-3 and IL-6. After 3 days, actively proliferating immunoblast-like B cells were apparent in 12/14 cases of MM, 0/3 BMG, 3/3 WM and 0/2 B-CLL. After 6 d, B blasts had evolved into morphologically evident plasma cells expressing the specific monoclonal light and heavy chains. The data indicate that the concerted action of IL-3 and IL-6 synergistically promotes the proliferation and differentiation of circulating plasmacell precursors in malignant monoclonal gammopathies.