Congenital infection by human cytomegalovirus (CMV) is presently the leading infectious cause of mental retardation and congenital deafness in the United States. Live CMV vaccines in healthy adults have been shown to be safe and to induce immune responses similar to those that occur with natural CMV infection. Yet, only recently has a live CMV vaccine been tested for its protective ability. To evaluate the cost benefit and effectiveness of the proposed live CMV vaccine, we compared the following strategies: routine immunization, selective immunization of those women screened and found to be seronegative, and no immunization. Our results show that, when direct costs alone are considered, routine immunization of healthy women aged 15-25 years is cost beneficial even in populations with CMV seroprevalence as high as 87%. In populations with lower seroprevalence (55%-70%), for every 100, 000 women immunized, more than 24 cases of symptomatic congenital CMV infection at birth and a similar number of cases with late sequelae (mainly deafness) would be prevented yearly. Such immunization would result in a net annual saving of $2.5 million.