On December 18, 2003, the Rhône Departmental Directorate of Health and Social Affairs (DDASS) reported five cases of invasive group A streptococcal infection (IGAS), including three deaths, with no obvious nosocomial origin and suspected community-acquired transmission. This unusual situation led to the implementation of active case finding between December 18, 2003, and February 13, 2004, in microbiology laboratories in the Rhône region by the Interregional Epidemiology Unit (CIRE) and the DDASS, in collaboration with the National Reference Center for Streptococci (CNR), the Institute for Public Health Surveillance (InVS), and the Directorate General of Health (DGS). The objectives of this investigation were to identify community-based clusters of cases, describe the cases, identify common risk factors, and detect the emergence of strains exhibiting particular virulence. A confirmed case of IISGA was defined as the identification, by a microbiology laboratory in the Rhône region since November 1, 2003, of a culture positive for Streptococcus pyogenes either in sterile fluid or at a site not typically sterile with soft tissue necrosis. A suspected case of IISGA was defined as the identification, by a microbiology laboratory in the Rhône region since November 1, 2003, of a positive culture from a non-sterile site associated with a compatible clinical picture of infection and no other identified cause. In total, 25 confirmed cases and one suspected case were identified over a 12-week period. Nine people had developed toxic shock, and four of them had died. Seven cases were children under the age of 10. Eight women were postpartum or post-abortion cases. Twenty-two people resided in the Rhône department, three in neighboring departments, and one person was visiting the Rhône department. The geographic distribution of the cases’ residences showed no link between the cases. The incidence of cases appeared higher in the western part of the Lyon metropolitan area, but spatial analysis using a Poisson model did not reveal any geographic clusters. Data from the Epibac surveillance network for community-acquired invasive infections over the past three years confirmed the occurrence of an unusual number of cases in the Lyon region. Six cases were confirmed nosocomial cases, and one was a suspected case. With the exception of one confirmed case and the suspected case, which occurred in the same facility and were linked (the suspected case being the index case for the confirmed case), the nosocomial cases occurred in different facilities. Microbiological analyses did not reveal the existence of a common strain among the cases but showed that the increase in cases was accompanied by an increase in two types of strains: T1M1 and T28M28. The latter is comparable to the emerging emm28 clone observed in France since 2000. A joint investigation by the Southeast Regional Coordination Center for the Control of Nosocomial Infections (C-Clin) and the Ddass was conducted at the healthcare facility that reported 6 cases, including the 2 confirmed nosocomial cases and related suspected cases. Since the investigation results did not reveal any clusters of community-acquired cases, active case surveillance was discontinued on February 13, 2004. However, the microbiology departments of the Hospices Civils de Lyon were asked to send the CNR the isolates from all HAI cases, and facility directors were instructed to report any cases occurring in a maternity ward. Recommendations were also reiterated to healthcare facilities to prevent the occurrence of postpartum cases. (R.A.)