OBJECTIVE To evaluate the antibody response to a Haemophilus influenzae type b capsular polysaccharide (HibCP) tetanus toxoid (TT) conjugate vaccine (HibCP-TT) in preterm infants. METHODS Thirty-five healthy preterm infants with gestational ages (GA) from 27 to 36 weeks and birth weights from 920 to 2550 g. Controls were 37 term infants. METHODS All infants were immunized with HibCP-TT at 2, 4 and 12 months of age. Antibodies to HibCP and TT were determined at each immunization and 1 month after the second and third. RESULTS After two doses of HibCP-TT the preterm infants with GAs < or = 30 weeks (n = 8; mean GA, 29.5 weeks) had a significantly lower HibCP antibody response than the preterm infants with GAs > 30 weeks (n = 23; mean GA, 34.2 weeks) (P = 0.004), who for their part had a response not significantly different from that of the term infants. After the third dose there were no significant differences among the groups. The response to the TT part of the vaccine showed the same pattern. CONCLUSIONS Although the most immature infants may show an inadequate antibody response to the initial immunizations, many preterm infants can benefit from vaccination with HibCP-TT when starting immunization at the same chronologic age as term infants.