Primary cytomegalovirus (CMV) infection during the first half of pregnancy is responsible for the majority of symptomatic congenital infections. Between one-third and one-half of fetuses become infected, and up to one-half of infected fetuses will have neurologic or sensorineural sequelae at birth or later in life. Following favorable results obtained in animal experiments, observational studies have shown beneficial effects after administration of high-titer CMV hyperimmunoglobulin to pregnant women with fetal infection or disease subsequent to primary CMV infection. The mechanisms of action of hyperimmunoglobulin are multiple and not yet fully understood. However, they could reside in 2 major properties: (1) antiviral activities due to high-avidity neutralizing antibodies and (2) immunomodulating activities mostly including downregulation of cytokine-mediated cellular immune responses. A decreased viral pathogenicity occurs as an immediate consequence, whereas reduced placental inflammation and restored function are the long-term effects.