A primary maternal infection with cytomegalovirus (CMV) either during or just before pregnancy accounts for the majority of congenital infections where the baby is symptomatic at birth. Following a primary maternal infection, depending on gestational age, between one quarter and three quarters of fetuses will become infected, and approximately one-third of infected fetuses will have symptoms at birth. Experiments using animal models of CMV infection and observational studies in humans indicate that administration of a CMV hyperimmune globulin (HIG) to the pregnant woman with a primary CMV infection should be effective for both the treatment and prevention of fetal infection. The HIG probably acts by reducing placental inflammation, neutralizing virus with high avidity antibodies, and perhaps by reducing cytokine mediated cellular immune responses.