The safety and immunogenicity of primary immunization at 2, 4 and 6 months of age with Haemophilus influenzae type b capsular polysaccharide conjugated to tetanus toxoid (PRP-T; Act-HIB) were evaluated in infants in Valencia, Venezuela. In order better to assess reactions to PRP-T, subjects received their initial PRP-T vaccine a mean of 6.5 days after their initial diphtheria-tetanus-pertussis (DTP) vaccine. The PRP-T vaccine was well tolerated. Serum was obtained at ages 2 and 7 months (before the first and 1 month after the third PRP-T dose). Antibody responses were compared with those from Nashville infants who had received PRP-T and DTP simultaneously in a previous trial. The preimmunization titers in the Venezuelan and Nashville infants did not differ. The geometric mean postimmunization titer in the Venezuelan infants was 37.9 micrograms/ml, as compared with 3.63 micrograms/ml in the Nashville infants (P < 0.00001). Possible explanations for the exceptional antibody response of these Venezuelan infants to PRP-T include carrier priming caused by prior DTP immunization, synergy associated with the specific DTP vaccine used, preimmunization immunologic experience that differed from their United States counterparts and genetic differences that altered response to the vaccines. Further studies are proposed to evaluate these possibilities.