Antibody responses to Haemophilus influenzae type b (Hib) conjugate (ActHIB; Pasteur Merieux) and pneumococcal (Pneumovax II; Morson) vaccines were measured in 56 infected children (VI) and 44 uninfected children (U) older than 18 months of age, born to human immunodeficiency virus-positive mothers. Preimmunization, 21% U and 20% VI had protective concentrations of anti-Hib polysaccharide antibodies. Postimmunization, 100% U and 86% VI achieved protective titers (P = 0.008). The geometric mean increase in anti-Hib polysaccharide antibody was 7.6 (95% confidence interval, 3.5 to 16.3; P = 0.0001) times higher in U than in VI children after adjusting for age and ethnicity. Sixty-one percent U compared to 54% VI showed a 2-fold increase in antibody levels to at least one of the four pneumococcal vaccine serotypes (3, 6, 19, 23) measured (P = 0.4). For both vaccines there was a significant trend toward poorer responses in children with acquired immunodeficiency syndrome but no correlation with age adjusted CD4 counts. These data suggest that human immunodeficiency virus-infected children should be immunized with these polysaccharide vaccines early in the course of their disease.