Safety and immunogenicity of a Haemophilus influenzae type b polysaccharide-diphtheria toxoid conjugate vaccine (PRP-D) was evaluated in infants seven to 14 months of age. PRP-D (80% of subjects) or saline placebo (20%) was randomly and blindly administered (two doses separated by two months). Incidence of mild reactions lasting less than 48 hr did not differ significantly between the placebo and vaccine recipients. Preimmunization levels of antibody to PRP were less than or equal to 0.15 micrograms/ml in 97% of subjects. A twofold increase in antibody concentration occurred in 88% of subjects following the first dose and in 99% following the second dose of vaccine. No change occurred in placebo recipients. Mean level of antibody and percentage of subjects with levels of antibody greater than or equal to 1 microgram/ml after vaccination increased with increasing age. Responses were related to vaccine lot but not to sex, race, or geographic location. Two doses of PRP-D in infants seven months of age and older induced antibody levels equal to or greater than levels in infants 24 months of age given the polysaccharide alone.