Monoclonal antibodies to Haemophilus influenzae type b were produced by fusing splenic lymphocytes from immunized C57BL/6 mice with the mouse myeloma line P3-X63-Ag8.653. The antibody produced by one hybridoma (5M1H9) bound the capsular polysaccharide, as determined by a radiolabeled antigen-binding assay. The antibody was of the IgM class and was bactericidal in vitro with complement. The protective and therapeutic capacity of antibody 5M1H9 was examined in the infant rat model of H. influenzae type b disease. Antibody (0.1 ml), either undiluted or diluted 1:2, 1:10, or 1:100, administered 4 hr before intraperitoneal injection of 10(4)-10(5) H. influenzae type b organisms protected 100%, 90%,. 55% and 10% of the animals, respectively. To determine the efficacy of antibody 5M1H9 in treating established infection, antibody was given at 24-hr intervals after intraperitoneal injection of bacteria. Delayed administration of antibody 5M1H9 was effective in reducing both the level and incidence of bacteremia.