Infection of the fetus with cytomegalovirus (CMV) results in approximately 8,000 infants born each year who will be mentally retarded and/or deaf. These effects are mainly due to primary maternal CMV infection during pregnancy. We and others have found that between 25% and 80% of children acquire CMV infections in daycare and shed the virus for between 3 and 41 months (mean of 18 months). At least half of seronegative mothers with infected children under age 2 years acquire CMV from their children within one year compared to an annual rate of < 5% among other seronegative women. CMV vaccines with the potential to control this infection are available for evaluation. An effective national vaccination strategy to prevent primary maternal infection during pregnancy should include childhood immunization. In adults we found that natural seropositivity protects against reinfections. To determine neutralizing antibodies are effect the natural history of CMV infection in toddlers, we will evaluate a purified protein vaccine, CMV gB/MF59, in an expanded placebo controlled double blinded phase I-II safety and immunogenicity trial. Because the infants in this study will be enrolled in daycare and will have a high rate of primary CMV infections we will be testing the hypothesis that immunized children less than two years of age are protected against infection or have a reduced duration of viral excretion and one or the other of these will be associated with high levels of neutralizing antibodies. We will compare the infection rate or the duration of viral excretion of infants under two years of age enrolled in daycare and immunized with CMV gB/MF59 vaccine to the infection rate and duration of viral excretion of matched seronegative infants receiving a placebo. We will also determine if infection or the duration of viral shedding are associated with an infant's immune response or age. The parameters of the immune response to be measured will include IgG, IgG to CMV gB, neutralizing titers, IgG responses characterized by immunoblotting, CD4+ responder cell frequencies, and mucosal immunity. The results of this study will establish if prevention of CMV infections is possible. ? ?