This study describes the course of an outbreak of community-acquired Staphylococcus aureus (S. aureus) skin infections carrying the genes encoding Panton-Valentine leukocidin (PVL(+)) among students at a school and their family members, as well as the control measures implemented, including screening and treatment of nasal colonization by PVL(+) SA. Following reports of numerous Sa PVL(+) abscesses and boils at an elementary school, the Val-d'Oise Regional Health Authority conducted a retrospective investigation of skin infection cases and organized surveillance for new infections among students, their family members, and teachers. After screening the entire study population (n=357) for nasal colonization with Sa PVL(+), treatment with a mupirocin-based nasal topical was offered to colonized individuals. Additional screenings were conducted in families where new skin infections occurred. As of October 31, 2008, 53 individuals had developed 69 Sa PVL(+) skin infections in four successive waves of decreasing magnitude. The cumulative incidence of a first skin infection was 34.6% in elementary school, 21.3% in preschool, and 6.5% among the students’ family members. The prevalence of nasal colonization by Sa PVL(+) was 7.3% (25/339). Persistent colonization was observed in one-third of individuals who had been prescribed intranasal mupirocin. In families where new skin infections appeared, the frequency of nasal colonization was 14.1% among those screened a second time and 19.5% among those screened a third time. In an open setting, such as a school, early reporting of clusters of skin infections is necessary. (R.A.)