Nasal colonization by Staphylococcus aureus is an important risk factor for the development of a nosocomial infection. Acquisition of nasal colonization by S. aureus increases mortality in hospitalized patients, but little is known about the transmission dynamics of S. aureus. To study S. aureus transmission, colonization and colonization persistence, we developed a murine transmission model. In 20 cages, 2 out of 10 mice were nasally inoculated (at 5×10(8) c.f.u. per mouse) with either meticillin-susceptible S. aureus (MSSA) (10 cages) or meticillin-resistant S. aureus (MRSA) (10 cages). On days 5, 15, 25 and 40, all mice in a cage were swabbed or sacrificed and nasal colonization and c.f.u. were determined in all 10 mice by nasal dissection or by nasal swab. Spread and subsequent stable colonization by both MSSA and MRSA from colonized to uncolonized mice within a cage was seen. At day 5, an increased number of colonized mice were observed in the MSSA group compared to the MRSA group (P = 0.003). On day 40, the mean number of c.f.u. per mouse was higher for MRSA than for MSSA (P = 0.06). Faecal-oral transmission was shown to be a possibly important transmission route in this model. These results suggest a more rapid spread of MSSA compared to MRSA. However, MRSA shows a more stable nasal colonization after a longer period of time.