BACKGROUND: Cystic fibrosis (CF) patients can become persistently colonized with Staphylococcus aureus. This is initiated at an early age and may continue until or sometimes even during adolescence. Little is known about the epidemiology and cross-infectivity of S. aureus in CF patients, whether via the environment or person to person. METHODS: S. aureus isolates (n=189) from six unrelated CF patients and six pairs of CF siblings were genetically typed by arbitrary primed polymerase chain reaction (AP-PCR) assays. RESULTS: This longitudinal study revealed 35 different genotypes among the 189 isolates; the median number of types in a patient was three (range 1--6). One common S. aureus genotype was found in six patients and involved 20% of all isolates analyzed. Ultimately, in most of the patients long-term colonization with a single genotype was observed. In several, but certainly not all, pairs the siblings became persistently colonized with isolates that could not be discriminated by the typing method used; different S. aureus genotypes were isolated on an incidental but relatively frequent basis. Only one pair of siblings never shared identical isolates at any time during the screening period. CONCLUSIONS: In five of six cases, identical isolates were shared by CF siblings at a certain time. This suggests intra-family transmission or the presence of a common environmental source. The fact that in most of the CF sibling pairs different genotypes of S. aureus caused the ultimate long-term colonization indicates that, despite regular cross-colonization, patient characteristics select the S. aureus strain best adapted to the affected lung. Some genotypes may be particularly prevalent in the CF patient population, but additional studies are needed to confirm this.