Reducing oligosaccharides from the Haemophilus influenzae type b capsular polymer (PRP) coupled by reductive amination to diphtheria toxoids (DTd) had been shown to elicit potentially protective serum anti-PRP antibodies (Ab) in infants too young for an adequate response to PRP vaccine. Here we report that cleavage of PRP with periodate gives antigenic oligosaccharides that couple with high efficiency. DTd-coupled saccharides of mean length eight or 20 repeat units (Dpo8 and Dpo20, respectively) were tested for immunogenicity in young adults (single injection) and in infants 9 to 15 mo old who received a sequence of primary (1 degree) and secondary (2 degrees) injections. Both vaccines consistently induced high anti-PRP Ab responses in adults. In infants, Dpo8 elicited only modest anti-PRP responses, whereas Dpo20 gave consistently high titers; post-2 degrees responses were higher when the interval between 1 degree and 2 degrees injections was 6 to 14 wk than with an interval of 2 to 4 wk. Thus with this type of immunogen, priming responses in infancy has more stringent structural requirements than does triggering responses in adults, and the priming appears to maximize more slowly than the Ab level.