Sera from populations of normal adults and children as well as sera from children with systemic Haemophilus influenzae type b disease were tested for antibodies reacting with ribosomes from H. influenzae type b. Adults generally had high titers of antibody, with 90% having titers greater than 1:64. The distribution of titers approximated a normal curve. Among normal children, there was more variability between individual titers, with the median titers ranging between 1:64 and 1:128. In contrast, acute-phase sera from children with systemic H. influenzae type b disease all had titers of 1:16 or less. Two convalescent-phase sera had high titers. Absorption experiments ruled out cross-reaction between ribosomes and type b capsular material. Ribosomes from two unrelated type b strains were completely cross-reactive, whereas absorption with ribosomes from a type c strain led to significantly decreased titers in three of four sera. Absorption of sera with ribosomes from Pseudomonas aeruginosa and Streptococcus pneumoniae also decreased titers, indicating that these antibodies may have been induced by ribosomes of other bacteria.