• Based on evidence that patients with infections due to Haemophilus influenzae type b (HIB) remain colonized after therapy, recommendations for chemoprophylaxis of susceptible contacts have included providing rifampin for patients themselves. However, these recommendations have been made with neither definitive advice concerning the timing of rifampin administration nor any supporting data of efficacy and safety in patients. Our data suggest that rifampin given concurrently with therapeutic antimicrobials is as effective—89% (17/19)—as when given following therapeutic antimicrobials—95% (18/19)—in eradicating pharyngeal HIB. Colonization of the pharynx by HIB was also determined before and during therapy. Almost all patients were colonized before beginning therapy; most were heavily colonized. The density of colonization diminished rapidly during the first 15 to 20 hours of therapy. However, 28% of patients, primarily those who had HIB diseases other than meningitis or did not receive any chloramphenicol, still had detectable colonization after four to six days of antimicrobial therapy.