In late February 2005, the French Institute for Public Health Surveillance was notified by the National Reference Center for Salmonella of an increase in the number of Salmonella enterica serotype Agona strains isolated from infants in January and February 2005. An epidemiological investigation was launched to confirm the existence of an outbreak, assess its magnitude, identify its source, and propose appropriate control measures. A case was defined as an infant residing in France who, since January 1, 2005, had tested positive for Salmonella Agona in connection with a fever or diarrhea. Starting on March 3, the families of the cases were interviewed regarding symptoms, foods and beverages consumed during the 7 days preceding the onset of clinical signs, the presence of diarrhea cases among close contacts, and the method of preparing and storing baby bottles. To investigate the suspected food source identified by the initial interviews, a case-control study was conducted involving the first 23 cases and 23 control infants. Human, food, and environmental strains of Salmonella Agona were compared using pulsed-field gel electrophoresis (PFGE). On March 4, the case-control study showed that all cases had consumed Picot brand infant formula and that none of the controls had consumed it (p<0.00001). No other food was associated with the onset of the illness. The immediate recall of Picot-brand infant formula was followed by a rapid decline in the number of cases involving consumption of this formula, but by an increase in the number of cases involving consumption of Blédilait-brand infant formula. Five batches of Blédilait infant formula had been manufactured on the same production line as the Picot infant formula. A total of 146 cases were identified between January 4 and June 3, 2005: 44 (31%) linked to the consumption of Picot milk powder and 92 (65%) to Blédilait milk powder. Salmonella Agona was isolated in one of the 176 samples of Picot milk powder analyzed, in 6 of the 420 samples collected from the environment of the Picot milk powder manufacturing and packaging lines, and in 4 of the 27 boxes of Blédilait milk powder collected from the families of the cases. These food and environmental strains had the same PFGE profile as 82% of the strains isolated from cases. This is the first documented outbreak of Salmonella Agona infections in France. This investigation demonstrated the inadequacy of in-house Salmonella testing in milk powders for detecting low-level and heterogeneous contamination. It also highlights the importance of investigating all cases to assess the effectiveness of control measures. (R.A.)