The immunogenicity of a vaccine formulation consisting of recombinant-derived human cytomegalovirus (HCMV) glycoprotein B (UL55) combined with a chemically defined adjuvant derived from saponin, QS-21, was evaluated in mice. The immune responses of mice given the gB/QS-21 formulation were compared with those induced by gB combined with either Freund’s adjuvant or aluminum hydroxide. The gB/QS-21 combination induced higher levels of virusbinding antibodies and significantly higher levels of virus-neutralizing antibodies than gB combined with either Freund’s adjuvant or aluminum hydroxide. Animals given gB/QS-21 exhibited IgG subclass switching and produced significant titers of virus-specific IgG2a antibodies. Furthermore, animals given gB/QS-21 produced antigen-specific cytotoxic spleen cells. Because of its immunogenicity, a subunit vaccine containing HCMV gB and QS-21 offers a potential approach to the immunoprophylaxis of HCMV disease. © 1995 by The University of Chicago.