We studied the immunologic responsiveness to Haemophilus influenzae type b capsular polysaccharide-Neisseria meningitidis group b outer membrane protein conjugate vaccine (PRP-NOMP) in children 2 to 42 months of age with vaccine dosages containing 7.5, 15, or 30 micrograms of PRP. Overall, PRP-NOMP was highly immunogenic. Geometric mean titers of anti-PRP antibody increased from 0.09 to 3.3 mg/L and 6.6 mg/L following each dose of vaccine, respectively, in the 2- to 18-month age group. Similarly, anti-PRP antibody geometric mean titers increased from 0.12 to 5.9 mg/L in the older than 18-month age group. However, we noted an apparent inverse relationship between vaccine dosages and immune responses following two doses of PRP-NOMP in 2- to 18-month-old children. Anti-PRP antibody geometric mean titers were 12.0, 6.9, and 3.5 mg/L, respectively, after the second dose of vaccine containing 7.5, 15, or 30 micrograms of PRP. Additional studies are needed to understand the mechanisms responsible for this inverse relationship and also to determine the optimal dosage of PRP-NOMP for young children.