Meningitis due to Haemophilus influenzae serotype b biotype II occurred in a 2-year-old child who attended a nursery school along with 26 other 2-year-old children. Nasal swabs from these 26 contacts revealed a H influenzae type b colonization rate of 50% (13/26); simultaneously performed throat swabs detected a colonization rate of 4% (1/26). Biotyping of the H influenzae type b isolates revealed that only 46% (6/13) were the same biotype as the index case; the remaining seven isolates were biotype III. All children received treatment with 20 mg/kg/day of rifampin administered by the nursery school attendant as a single dose for four days before the results of the cultures were known. Eradication of H influenzae type b carriage was successful in three of the six biotype II carriers and five of the six biotype III carriers available for follow-up culture. It was concluded that: (1) the culture site utilized in determining H influenzae type b colonization rates may markedly influence the results obtained; (2) biotyping may be a valuable epidemiologic tool in investigating the contacts of patients with H influenzae type b disease, and (3) failures of rifampin to eradicate the carriage of H influenzae type b from the nasopharynx may occur. The prudent approach to the management of young contacts of patients with serious H influenzae type b disease is to recognize their high risk status and to maintain close surveillance of them. The role of chemoprophylaxis with rifampin remains to be established.