The immunogenicity of Haemophilus influenzae type b polysaccharide-protein conjugate vaccines in congenitally asplenic children is unknown. The short-term immunogenicity of the H. influenzae type b polysaccharide-diphtheria toxoid conjugate vaccine was therefore assessed in 10 children with congenital asplenia by measuring antipolyribosyl-ribitol phosphate antibody titers. An excellent antibody response was seen in 9 children (mean geometric titer in responders after immunization 44.7 micrograms/mL; range, 2.59-402). The remaining child responded to a booster dose. Further studies are required to assess whether H. influenzae type b conjugate vaccines are immunogenic in infancy in the presence of congenital asplenia.