In June 2009, the first cluster of 2009 influenza A (H1N1) cases in France, with no history of travel, was reported in a 6th-grade class on the outskirts of Toulouse. A retrospective cohort study was conducted using standardized questionnaires and virological testing (nasopharyngeal swabs) among the students and 8 adults involved in the class, to describe the outbreak and analyze the sensitivity of the clinical definition of a probable case of influenza A (H1N1) 2009. A probable case was defined as any student or staff member in the class who had at least one general symptom (fever, fatigue, or body aches) and at least one respiratory symptom (cough, shortness of breath) since June 1, 2009. A confirmed case was a person with a positive PCR test for 2009 influenza A (H1N1). Active case finding was conducted among close contacts of the students and staff in the class. Between June 10 and 14, 18 of the 30 students met the definition of a possible case (60% attack rate), and 15 met the definition of a confirmed case, 20% of whom were asymptomatic (3/15). No chain of transmission was identified. Using PCR as the gold standard, the sensitivity of the clinical definition of a probable case was 47% and its specificity was 80% among students. Sensitivity was 80% when headache and rhinorrhea were added to the case definition. This investigation highlighted a significant proportion of asymptomatic cases and the low sensitivity of the case definition among children, which were poorly understood at that time. This epidemic, which was not linked to travel, was a landmark event in France. It contributed to shifting the surveillance of the 2009 influenza A (H1N1) epidemic from monitoring imported cases to population-based surveillance. (R.A.)