Infant rats inoculated intraperitoneally with Haemophilus influenzae type b develop bacteremia and meningitis. Rats were infected at 10 to 12 days of age and studied for the development of serum anticapsular antibody and bactericidal and opsonizing activity. Seven and 11 weeks after inoculation, convalescent animals showed a higher frequency of anticapsular antibody responses than uninfected controls, but 35 to 40% of the infected group had undetectable levels of anticapsular antibody (<0.10 mug/ml). In contrast, all of the convalescent animals, but none of the controls, showed moderate titers of serum bactericidal activity; and bactericidal activity persisted after absorption of the convalescent sera with type b capsule. Bactericidal activity was detected primarily in the eluted fraction corresponding to a molecular weight of 150,000 and was present in the offspring of convalescent females. Offspring of convalescent females were protected against challenge with H. influenzae type b, and control offspring could also be protected by passive immunization with convalescent serum which lacked detectable anticapsular antibody. Convalescent serum samples efficiently opsonized H. influenzae type b, and this activity persisted after absorption of the serum with capsular antigen. These data are consistent with the hypothesis that antibody to the noncapsular surface antigens of H. influenzae type b play an important role in host defenses.