During routine surveillance of patients in a Neonatal Intensive Care Unit (NICU), an alert infection-control practitioner confirmed the relationship of the index patient (sibling 3) who had a methicillin-resistant Staphylococcus aureus (MRSA) infection to an infant sibling (sibling 2) who had been admitted to the hospital 7 months previously with an MRSA infection. Cultures of nasal specimens obtained from the index patient's parents and two other siblings also yielded MRSA for two of the family members, the mother and sibling 1. The strains were typed by antibiogram, plasmid analysis, and genomic DNA typing. The isolates from sibling 1, sibling 2, the mother, and one isolate from sibling 3 were found to be identical by all techniques. The other isolates from sibling 3 shared the same genomic type but had no detectable plasmids. These findings suggest that transmission of this strain occurred at least three times within this family and that at least one family member was colonized with the same strain for 7 months or more. Recognition that family members may serve as reservoirs for nosocomial infections with MRSA raises important issues for infection control.