P>The Staphylococcus aureus immune evasion cluster (IEC), located on beta-haemolysin-converting bacteriophages (beta C-Theta s), encodes the immune-modulating proteins chemotaxis inhibitory protein, staphylococcal complement inhibitor (SCIN), staphylococcal enterotoxin A and staphylokinase. Its precise role in S. aureus colonization is unclear. We studied the presence of the IEC-carrying bacteriophages in human and animal S. aureus isolates, using PCR for the gene encoding SCIN (scn). Human isolates were obtained by collecting serial nasal swabs from 21 persistent carriers. S. aureus strains from 19 (90%) persistent carriers contained an IEC that was present and indistinguishable in 95% of cases at all five sampling moments over a 3-month period. Of the 77 infectious animal strains included in the study, only 26 strains (34%) were IEC-positive. Integration of these IEC-positive strains into an amplified fragment length polymorphism genotype database showed that 24 of 53 (45%) strains were human-associated and only two of 24 (8%) were 'true' animal isolates (p < 0.001). The high prevalence and stability of IEC-carrying beta C-Theta s in human strains suggested a role for these beta C-Theta s in human nasal colonization. To test this hypothesis, 23 volunteers were colonized artificially with S. aureus strain NCTC 8325-4 with or without the IEC type B-carrying beta C-Theta 13. Intranasal survival was monitored for 28 days after inoculation. The strain harbouring beta C-Theta 13 was eliminated significantly faster (median 4 days; range 1-14 days) than the strain without beta C-Theta 13 (median 14 days; range 2-28 days; p 0.011). In conclusion, although IEC-carrying beta C-Theta s are highly prevalent among human colonizing S. aureus strains, they are not essential in the first stages of S. aureus nasal colonization.