On May 10, 2005, the Rhône Departmental Health and Social Affairs Directorate (DDASS) received seven reports of cases of Legionnaires' disease diagnosed at the Croix Rousse Hospital (Hospices Civils de Lyon) involving residents of the northern part of the Lyon metropolitan area. Immediate efforts to raise awareness of the diagnosis were undertaken among hospitals, clinics, physicians, and laboratory technicians in the area, along with a descriptive epidemiological investigation and an environmental investigation. In total, 34 cases of Legionnaires’ disease were identified in the northern part of the Lyon metropolitan area between April 28, 2005, and May 9, 2005. Twenty-seven were hospitalized; none died. The epidemiological investigation conducted by the Rhône and Ain Departmental Health Services (DDASS) with support from the Regional Health Agency (CIRE) showed that at least 31 of the 34 cases resided in or had visited the municipalities of Caluire-et-Cuire and/or Rillieux-la-Pape. The presumed period of contamination for the cases spanned, at most, from April 18 to May 7. All cases were diagnosed based on positive urinary antigen testing (Legionellosis caused by Legionella pneumophila serotype 1). The three clinical strains isolated were identical to one another and corresponded to an endemic strain in France, listed in the CNRL. A systematic survey of operators of cooling towers in the municipalities of Caluire-et-Cuire, Rillieux-la-Pape, and within a 5-kilometer radius was undertaken starting May 11, led by the DRIRE. Seventeen sites with towers in operation or containing water in April 2005 were gradually identified in this area. Samples were systematically collected and the towers shut down. Legionella pneumophila was found at 5 sites, but the genomic profiles of the 13 isolated strains differed from those of clinical strains. Other facilities capable of producing aerosols in the municipalities of Caluire-et-Cuire and Rillieux-la-Pape were investigated. A communal sprinkler system (vegetable farming and horticulture), misters in fruit and vegetable stores, car wash stations, and a spa in a home improvement store were identified. Despite a link to these facilities in only a minority of cases and their a priori limited dispersal potential (apart from the irrigation systems), the facilities were shut down and samples were collected. Legionella pneumophila was found at 3 facilities, but the genomic profiles of the 11 isolated strains differed from the profile of the clinical strains. Other sources of aerosol emissions in Caluire-et-Cuire and Rillieux-la-Pape, as well as cooling towers located outside these municipalities, did not appear to be the source of the outbreak (sources were too localized or too far from the locations frequented by the majority of cases). In hindsight, the source of contamination had likely ceased emitting Legionella before the outbreak was detected and control measures were implemented. However, this outbreak served as an opportunity for a strong mobilization of government agencies, particularly for the identification of cooling towers within a targeted geographic area. It is important to capitalize on this momentum to continue the active inventory of cooling towers in the Lyon region. Furthermore, this outbreak served as a reminder of the importance of early reporting of Legionnaires’ disease cases, the value of clinical samples for isolating strains, and, finally, the need for effective coordination among local, regional, and national stakeholders during investigations. (R.A.)