Staphylococcus aureus, a major source of nosocomial and community-acquired infections, has a nasal carriage rate exceeding 25% in the human population. To elucidate host-pathogen interactions pertaining to nasal carriage, we examined the role of interleukin-1 (IL-1) in the colonization of human nasal epithelial cells (NEC) by a nasal carrier strain and a non-carrier strain of S. aureus. Using an organotypic model of the nasal epithelium, we observed that inoculation with a non-carrier strain of S. aureus induced production of IL-1 from NEC, but the expression of this cytokine was significantly reduced when NEC were inoculated with a carrier strain. Moreover, both IL-1alpha and IL-1beta significantly decreased the growth of the nasal carrier strain of S. aureus (P < 0.001, n = 17 to n = 25); however the growth of the non-carrier strain was unaffected. Interestingly, it was found that several nasal carrier strains of S. aureus form quorum-dependent biofilms, which can be partially inhibited when preincubated with IL-1alpha. Taken together these data suggest that, although nasal carrier strains of S. aureus are sensitive to IL-1, they display a significant colonization advantage by both preventing the host from expressing IL-1 and elaborating a protective biofilm.