Human interleukin-6 (hIL-6) injected into mice increases antigen-specific antibody production. In the present study, we examined the possibility that anti-hIL-6 murine monoclonal antibody (MH-166) could neutralize this hIL-6 activity in vivo. Although MH166 completely neutralized hIL-6 activity in vitro, treatment in vivo with hIL-6 and MH166 combined unexpectedly increased both anti-dinitrophenyl (DNP) and anti-sheep red blood cell (SRBC) antibody production more than treatment with IL-6 alone did. To explain this phenomenon, the serum hIL-6 level was monitored following the MH166 administration. The hIL-6 level was significantly higher in the mice treated with both hIL-6 and MH166 than in the mice treated with hIL-6 alone during the 24 hr following hIL-6 administration. These results indicate that MH166 prolongs half-life of a xenogeneic hIL-6.