The mechanism of antibody-mediated reduction of Haemophilus influenzae type b (Hib) carriage was studied in the infant rat colonization model. Monoclonal Hib polysaccharide (PS) antibody (MAb) given intranasally or intraperitoneally and human secretory anti-Hib PS IgA given intranasally inhibited colonization by Hib during the entire follow-up period (2-48 h after challenge) but did not affect colonization by Hi, a noncapsulated variant of Hib. Ftab'), fragments, prepared from the MAb or from human serum anti-Hib IgG reduced Hib colonization as efficiently as the unc1eaved molecules. Complement depletion by cobra venom treatment had no effect on the antibody-mediated reduction of Hib colonization. These results indicate that Fc-mediated activities of immunoglobulins are not essential in the reduction of Hib colonization. Instead, antibodies to Hib most likely reduce colonization by a direct effect on growth of the bacteria or their adherence to the nasopharyngeal mucosa.