Background: Outbreaks of pneumococcal infection have been rare during the antibiotic era. In October 1996, three children attending the same day care center (DCC-A) developed multidrug resistant Streptococcas pneumoniae (MDRSP) meningitis over a 5-day period; one died. Methods: Nasopharyngeal (NP) swabs were collected for culture from 82 of 86 children. Because of the ongoing nature of the outbreak, children at DCC-A were given a 7-day course of rifampin and clindamycin prophylaxis. NP swabs also were performed on 98 children in two other local DCCs (DCC-B and DCC-C). Isolates were subtyped by pulsed field gel electrophoresis (PFGE). Results: All three children were infected with MDRSP serotype 14 resistant to penicillin (minimum inhibitory concentration [MIC] 4.0 μg/ml) and intermediate to cefotaxime (MIC 1.0 μg/ml), indistinguishable by PFGE. NP cultures revealed a 64% pneumococcal carriage rate among children at DCC-A compared to 48% at DCC-B and 44% at DCC-C. At all three DCCs, 15-20% were colonized with MDRSP serotype 14. All MDRSP serotype 14 isolates tested from DCC-A and DCC-B had the same PFGE pattern as the children with meningitis, but all from DCC-C had a distinct pattern. NP swabs were collected from children at DCC-A at 4, 32, and 103 days after completion of chemoprophylaxis; MDRSP serotype 14 was still carried by 4%, 19%, and 8% of children, respectively Conclusions: This outbreak demonstrates the potential for MDRP to cause epidemic illness. The intervention chosen, although possibly effective at preventing additional cases, did not prevent rapid recolonization. PFGE demonstrated that the outbreak strain was widely disseminated in the community, but not as widely as would have been assumed on the basis of serotyping and antimicrobial susceptibility testing alone.