The objective of this double-blind, randomized, placebo-controlled Phase II study is to determine whether a recombinant subunit vaccine comprised of cytomegalovirus (CMV) envelope glycoprotein B (gB) with MF59 adjuvant can prevent maternal CMV infection between pregnancies in a high risk population of women of childbearing age. This study will also permit determination of whether the approach used is a feasible one for a large scale efficacy trial with prevention of congenital CMV as the endpoint. CMV gB vaccine is comprised of a recombinant CMV envelope glycoprotein produced in a Chinese hamster ovary cell line. The CMV gB is combined with a novel adjuvant, MF59, a proprietary oil-in-water emulsion. Vaccines will be administered at 0, 1, and 6 months by intramuscular injection in the left deltoid. Placebo recipients will be given a normal saline solution. Study participants were recruited from postpartum wards and from the community. Potential participants were screened for antibody to CMV; those who were seronegative were invited to participate in the vaccine study. Participants received their initial immunization 1.5 to 12 months postpartum. A total of 464, seronegative women who were willing to participate and met enrollment inclusion and exclusion criteria were randomized to 1 of 2 groups: Group I participants received 20 micrograms of gB with MF59; Group II participants received placebo (normal saline). During the immunization period local and systemic reactogenicity was assessed by a 7-day diary card completed after each dose of vaccine. Adverse events are tabulated. Safety is assessed by comparing the local and systemic reactogenicity and adverse event rates between vaccine and placebo recipients. Study participants are screened for CMV infection every three months, beginning three months after the first dose of vaccine, using a CMV IgG antibody assay with preabsorption of sera with purified recombinant CMV gB (vaccine antigen). CMV infection will be confirmed by either isolation of virus or detection of CMV DNA in body fluids. After the 3 dose vaccine schedule has been completed, participants are followed every 3 months. The primary endpoint is the time to CMV infection. The rate of congenital CMV infection in offspring of immunized mothers is a secondary endpoint. The rate of congenital CMV infection will be compared between offspring of vaccine and placebo recipients. Each subject will be followed for 3 years from the third dose of vaccine. Specific information will be collected on the following pregnancy outcomes: pregnancy report, pregnancy follow-up, abnormal pregnancy outcome-mother, and abnormal pregnancy outcome-infant.