The association between transplacentally acquired maternal antibodies and outcome in congenital human cytomegalovirus (HCMV) infection was investigated by analyzing antiviral antibodies in the cord blood from infants with permanent neurologic sequelae and from those without sequelae. Higher levels of antiglycoprotein B and neutralizing antibodies were observed in infants with sequelae. Infants with symptomatic infection and those with > or = 2 sequelae had higher levels of virus binding antibodies. No association between neutralizing titers and progressive hearing loss was noted. These results suggested that the development of sequelae following congenital HCMV infection was not associated with measurable deficits in the maternal antiviral antibody response. Higher levels of anti-gB and neutralizing antibodies in infants with sequelae also suggested that the natural history of this congenital infection is unlikely to be modified by the passive administration of antiviral antibodies in the postnatal period.