Human cytomegalovirus (HCMV)-specific antibody response was analyzed to determine its relationship with sequelae in children with asymptomatic congenital HCMV infection. IgG antibodies reactive with envelope glycoprotein gB were significantly higher in cord and maternal delivery serum of infants developing hearing loss than in those without any sequelae. Women of hearing impaired children had higher levels of serum anti-gB IgG and HCMV IgM at first prenatal visit (8–16 weeks gestation) than did those with children with normal hearing. Kinetics of the antibody response revealed that women with hearing impaired children had peak anti-gB and IgM response at the first prenatal visit compared with at or near delivery in mothers of normal children. These results suggested that women who delivered infants developing hearing loss had a more intense and prolonged antibody response, and factors such as early virus acquisition during pregnancy might contribute to the development of sequelae in asymptomatic congenital HCMV infection. © 1993 by The University of Chicago.