At 4 and 6 months of age, 118 infants were vaccinated with either one of two Haemophilus influenzae type b capsular polysaccharide-protein conjugate vaccines: 72 infants received the polysaccharide coupled to diphtheria toxoid (PRP-D group), and 46 infants received polysaccharide-derived oligosaccharides coupled to CRM197 protein, a nontoxic mutant form of diphtheria toxin (HbOC group). A third dose of the same vaccine was given to 40 children in the PRP-D group and 25 children in the HbOC group at 14 months of age. Antibodies to the H influenzae type b capsular polysaccharide were measured by Farr-type radioimmunoassay in serum samples taken before each vaccination and 1 month after the second and the third doses. Adverse reactions monitored by a questionnaire were mild. After two vaccine doses, the geometric mean concentration of antibodies to H influenzae type b polysaccharide increased from 0.07 micrograms/mL in the prevaccination samples to 0.63 micrograms/mL in the PRP-D group and to 4.32 micrograms/mL in the HbOC group. In the following 7 months, the geometric mean concentrations declined to 0.38 and 1.12 micrograms/mL, respectively. The booster dose given at 14 months elicited a strong antibody response in both groups (to geometric mean concentrations of 29.7 and 58.3 micrograms/mL, respectively). Both vaccines appear to be capable of immunologic priming by immunization in infancy.