To evaluate the possibility that immunization with a capsular polysaccharide vaccine decreases immunity in the immediate postvaccination period and renders an animal susceptible to invasive Haemophilus influenzae type b disease, we passively immunized infant rat pups with an immune globulin preparation, vaccinated them with an H. Influenzae type b capsular polysaccharide vaccine at a wide range of doses, and challenged them with H. influenzae type b given intraperitoneally. Bacteremia occurred in 89% of protected, vaccinated pups compared with 17% of protected, unvaccinated pups (p = 0.0001). In protected, vaccinated pups the rate of bacteremia resembled that in unprotected, unvaccinated control pups and did not vary with the dose of vaccine administered. The magnitude of bacteremia and the incidence of meningitis in protected, vaccinated pups exceeded that occurring in the protected, unvaccinated control animals, but these effects diminished with the dose of vaccine. Diminution of anticapsular antibody occurred in association with the largest doses of vaccine. We conclude (1) that the administration of H. influenzae type b capsular polysaccharide vaccine in infant rats is associated with a diminution of passively acquired anticapsular antibody immediately after vaccination and (2) that experimental challenge with H. influenzae type b at this time produces disease resembling that in animals not passively given protection.