Three cases of meningitis due to multidrug-resistant serotype 14 Streptococcus pneumoniae occurred at a day care center (DCC) over 5 days. Cultures of nasopharyngeal samples were done at the index DCC, 2 comparison DCCs, and a pediatrics practice. Isolates were serotyped and subtyped by pulsed-field gel electrophoresis (PFGE) with Sinai. Pneumococcal carriage rates ranged from 44%-65% at the 3 DCCs and 29% in the pediatrics practice. Carriage of multidrug-resistant serotype 14 S. pneumoniae was noted in 13%- 19% of children at the 3 DCCs. An outbreak strain was identified by PFGE at the index DCC and I other DCC; a closely related strain was found in the third DCC. Carriage of the outbreak strain was associated with being age 0-24 months, antibiotic use, upper respiratory tract infections, and otitis media. DCC contacts of the ill children were offered chemoprophylaxis with rifampin and clindamycin, which produced a profound but transient decrease in carriage. No additional cases occurred.