Two of 16 children (14 to 24 months old) in a day care center developed Haemophilus influenzae type B (HIB) meningitis within a 3-week period. One day after the first child was diagnosed 13 children and 5 personnel received rifampin. Two children received no rifampin because they had received the HIB vaccine. After the second child was diagnosed HIB carriage was detected in 3 of the 15 children and 2 of 43 family members but in none of the caretakers. All seven isolates were biotype 1 but outer membrane protein analysis revealed two strains. One child, who had received rifampin for only 2 days initially, and a sibling of another child carried a common strain. A second strain was recovered from: the first meningitic child; the second meningitic child and another child, both of whom had initially received rifampin (20 mg/kg for 4 days); and one HIB-vaccinated child and his father. After the second rifampin administration all carriers were free of HIB. One child who was not treated with rifampin (because he had been vaccinated for HIB) was the apparent source of reinfection for the day care group. These data emphasize that when rifampin prophylaxis is initiated it should be administered to all classroom contacts.