A monoclonal antibody (MAb) specific for interleukin-6 (IL-6) was generated by fusing SP2/0 cells with spleen cells from a mouse immunized with rat spleen cell derived plasmacytoma growth factor (rat PCT-GF). This MAb inhibited the growth of an IL-6-sensitive murine plasmacytoma clone, MD90, in the presence of the immunogen, rat PCT-GF. More interesting, however, this MAb demonstrated species cross-reactivity by neutralizing murine (recombinant and P388D1, cell line-derived) and human (recombinant) IL-6. IL-6 neutralization activity was also established in other IL-6 bioassays, such as the proliferation of spleen cells, plasmacytoma T1165, and a B-cell hybridoma 7TD1. IL-6 neutralization was overcome partially by increasing the concentration of PCT-GF. The MAb had no effect on PCT-GF-independent plasmacytoma KI81 proliferation. Plastic petri dish-bound MAb removed rmIL-6 activity. These results suggest that this MAb specifically binds IL-6 and neutralizes bioactivity of various PCT-GF, rmIL-6, and rhIL-6. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.