Asplenic children are at increased risk for serious infection with polysaccharide encapsulated bacteria including Haemophilus influenzae type b (HIB), Streptococcus pneumoniae, and Neisseria meningitidis. Immunization with polysaccharide vaccines is recommended for children undergoing splenectomy. In 1987 a new more immunogenic HIB vaccine was licensed in the US to replace the pure HIB polysaccharide vaccine that was licensed in 1985. This polysaccharide-conjugate vaccine consists of the HIB polysaccharide linked to a protein carrier, diphtheria toxoid. Therefore, we evaluated the immune response of children undergoing splenectomy to HIB-conjugate vaccine. Thirteen children (7 with Hodgkin's disease, 4 with idiopathic thrombocytopenia, 2 with hereditary spherocytosis) aged 3 to 19 years were immunized with HIB-conjugate vaccine prior to splenectomy and serum was obtained following splenectomy. In addition, 15 healthy control children aged 2 to 14 years were immunized with the pure polysaccharide HIB vaccine for comparison. The patients undergoing splenectomy who received the HIB-conjugate vaccine had a geometric mean IgG anti-HIB antibody concentration of 48,106 ng/mL versus 10,786 ng/mL for the control patients who received the pure polysaccharide vaccine (P = .01). The presumed protective level of antibody is 1,000 ng/mL and all children were well above this concentration. Therefore, we propose that children undergoing splenectomy be immunized with an HIB-conjugate vaccine. © 1992.