LZ-8, a new and recently discovered immunomodulator from Ganoderma lucidum, has been shown to have immunosuppressive activity in vivo and to be a member of the immunoglobulin superfamily. In this paper we examined the in vivo effect of LZ-8 on antibody production using the hepatitis B surface antigen (HBs Ag) in mice. LZ-8 had mitogenic activity in vitro towards spleen cells of C57BL/10 (B10) and C57BL/10BR (B10BR) as previously shown towards those of DBA/2 mice. B10 and B10BR mice produced anti-HBs Ag antibody by the twice sensitization of the antigen while intraperitoneal administration of LZ-8 twice weekly into the mice (8 and 12 mg/kg) greatly prevented the production of antibody to HBs Ag (83.3-96.8% inhibition). We further examined the effect of LZ-8 administration on mitogen responsibility of spleen cells and on the T-cell subset population in both the spleen and lymph node but no significant differences were observed between the LZ-8 treated and untreated mice. These results suggest that the immunosuppressive activities of LZ-8, previously shown, such as the prevention of systemic anaphylaxis and the Arthus reactions, were caused by the blocking of antigen-specific antibody production.