Interleukin-12 (IL-12) may be a beneficial adjuvant for augmenting vaccine efficacy against encapsulated bacteria such as Streptococcus pneumoniae and Neisseria meningitidis since it can stimulate production of interferon-γ (IFN-γ) and secretion of antibody isotypes that are efficient at mediating complement fixation and opsonophagocytosis. In this study, we demonstrate the ability of IL-12 to enhance murine antibody responses, particularly IgG2a levels, to both pneumococcal and meningococcal conjugate vaccines. Transfer of immune serum from mice immunized with the meningococcal conjugate vaccine and IL-12 resulted in increased survival times, whereas transfer of serum from mice immunized with the pneumococcal conjugate and IL-12 resulted in protection from death upon bacterial challenge. Although treatment with vaccine and IL-12 increased levels of IFN-γ mRNA, IL-12-mediated enhancement of antibody responses still occurred in IFN-γ-/- mice. The results demonstrate the effectiveness of IL-12 as an adjuvant for polysaccharide conjugate vaccines, especially the pneumococcal conjugate vaccine. © 2001 Elsevier Science Ltd.