Introduction - In 2005, the number of Legionnaires' disease cases rose sharply in the Alpes-Maritimes department, with 74 cases reported and an incidence rate of 7.42 cases per 100,000 inhabitants—nearly four times the national rate. In December 2005, in response to this situation, a technical group was established to monitor the situation and conduct an epidemiological and environmental investigation into the cases reported during the last quarter of 2005. The objectives of this investigation were to describe the cases, identify any clusters of cases, and search for a common source or sources of contamination. Method - A retrospective descriptive study was conducted on cases of Legionnaires’ disease residing in the Alpes-Maritimes department, reported to the DDASS as of January 11, 2006, whose diagnostic criteria were pneumonia with laboratory confirmation of Legionnaires’ disease caused by Legionella pneumophila serogroup 1 (isolation, seroconversion, direct immunofluorescence, or positive urinary soluble antigen) and whose onset of symptoms occurred between October 1, 2005, and December 31, 2005. Clusters of cases were investigated based on residential addresses, workplaces, and travel during the 14 days preceding the onset of symptoms. An active search for unreported cooling towers (CTs) and potentially high-risk facilities was conducted by the Departmental Directorate of Health and Social Affairs (DDASS), the Regional Directorate for Industry, Research, and the Environment (DRIRE), and the Municipal Health and Hygiene Service (SCHS) of the city of Nice. Regarding the TARs, the results of self-inspections conducted since September 2005 were requested, enabling a targeted inspection of certain installations based on a set of criteria including the results of the latest self-inspections, the power output, and the geolocation of the installation in relation to the residence of the cases. Finally, samples were also collected at the cases’ residences when the domestic hot water system warranted it. Results - In total, of the 34 cases that occurred in the last quarter of 2005 and reported as of January 11, 2006, 32 were confirmed and analyzed. The temporal distribution showed that cases occurred throughout the period, with two peaks in weeks 43 and 50. Forty-seven percent of cases occurred in October, and 56% resided in Nice. The case fatality rate was 17%. Legionella pneumophila serogroup 1 was identified in all cases, and the biological diagnosis was established based on urinary soluble antigen. Genomic profiles were obtained for only 4 clinical strains, all of which were distinct and not listed in the National Reference Center (CNR) database. Three spatio-temporal clusters of 5, 4, and 3 cases were identified. No environmental strains could be linked to these clinical strains. No common source of contamination was identified. Discussion - The increase in the number of Legionnaires' disease cases in the Alpes-Maritimes in 2005 led to the hypothesis of an outbreak. Indeed, an abnormal and unprecedented increase in cases was observed, with a peak in incidence in October. However, the investigation failed to identify a common source of contamination. Although several spatio-temporal clusters of cases were identified, the cases occurred throughout the entire period, and neither a common geographic location nor any specific exposure factor could be identified. Finally, all identified clinical strains were different. Nevertheless, the retrospective and delayed nature of the investigation relative to the onset of symptoms in certain cases may have hindered the identification of the source(s) of infection. Very few clinical strains were isolated, and none could be linked to an environmental strain. Conclusion and Recommendations - This study was conducted in a specific situation of increased incidence without a clearly demonstrated epidemic nature. Following this investigation, it appears necessary to reiterate that, for any case of Legionnaires' disease, a standardized questionnaire must be completed promptly to identify a potential cluster of cases and initiate epidemiological and environmental investigations. Communication with clinicians is necessary to reduce delays in diagnosis and reporting. Obtaining clinical and environmental strains and sending them to the Legionella National Reference Center (CNR) in Lyon for molecular typing is essential to identify a source of contamination. The selection of TARs to be monitored should be based on a range of factors, including georeferencing, which may be useful. Finally, enhanced communication among the various partners involved in the investigation is essential. (R.A.)