Prepregnancy human and guinea pig cytomegalovirus immunity reduces rates of congenital infection in subsequent pregnancies. Inbred JY-9 strain guinea pigs were used to study the role of hyperimmune anti–glycoprotein B (gB) serum in modification of congenital infection in early pregnancy. Significantly shorter duration of primary maternal viremia and fewer pregnancy losses occurred in passively immunized dams, compared with nonimmune dams. Placentas from recipients of negative control serum were smaller and had marked mononuclear cell infiltrates and focal necrosis and more viral foci than did those from recipients of anti-gB hyperimmune serum. Significantly higher intrauterine growth retardation occurred in pups of negative control serum recipients than in pups of passively immunized dams. Significantly higher proportions of pups and placentas from recipients of negative control serum were positive on viral culture than from passively immunized dams. Thus, anti-gB passive immunization decreased fetal infection and intrauterine growth retardation, shortened maternal viremia, and reduced pregnancy losses and placental inflammation and infection