Background. Hantavirus infections are present in northeastern France. Humans become infected by inhaling dust contaminated with rodent excreta. In February 2003, the National Reference Center (NRC) for Viral Hemorrhagic Fevers reported an increased number of infections. An investigation was initiated to confirm the excess of cases, describe them, and propose appropriate measures. Materials and Methods. Cases, identified by the NRC, were defined by suggestive clinical signs associated with Puumala IgM and IgG in patients residing in France. Clinical and epidemiological information was collected for each patient. Results. In 2003, 128 cases were identified, compared with 61 in 2002. The median age was 38 years, and 77% of cases were men; 82% were hospitalized. Patients resided in the northeastern quarter of the country, with significant clusters in the Ardennes and the Oise. Risk exposures identified included occupational activities (35%) (construction, forestry, and agriculture), wood handling (35%), gardening (29%), and outdoor recreation (14%). Conclusions. This investigation confirmed the excess of cases in 2003. The geographic distribution and risk exposures were consistent with those reported in previous investigations. Prevention of Hantavirus infections requires individual measures against rodents and exposure to contaminated dust aerosols. Information resources for healthcare professionals and the general public in at-risk areas are necessary to promote these measures.