Following the equine epidemic that occurred in 2000 in the Camargue region, a surveillance program was established in the departments of the Camargue (Bouches-du-Rhône, Gard, Hérault) in 2001 and, since 2002, in Corsica, to detect the circulation of West Nile virus (WNV) in mosquitoes, birds, horses, and humans. In 2001 and 2002, human surveillance did not detect any confirmed cases, but the avian and equine components showed low levels of viral circulation. On October 6, 2003, the National Reference Center (CNR) for Arboviruses reported a case of WNV meningoencephalitis in a patient residing in the Var department. A case of equine WNV encephalitis was reported on October 9 by AFSSA in a neighboring locality. The health authority decided to extend surveillance to all departments along the Mediterranean coast and to initiate an investigation into the Var case. Human surveillance aimed to identify severe cases of WNV infection. A “suspected case” was defined as a patient over 15 years of age, hospitalized between June 1 and October 1, 2003, in one of the departments of Camargue or Corsica—and expanded to all departments along the Mediterranean coast as of August 1—who presented with clear cerebrospinal fluid (CSF) collected due to a febrile state (fever > 38.5°C) associated with neurological symptoms. The investigation into the Var case, aimed at identifying the area and period of viral circulation, led to serological testing of individuals with less severe symptoms (“mild cases”) who did not meet the definition of a suspected case. A probable case was defined by the detection of anti-VWN IgM via ELISA. Cases were confirmed by seroneutralization. Of the 109 healthcare facilities included in the expanded surveillance, 53 participated (48.6%). Eighty cases were reported, of which 70 suspected cases were tested by the two reference laboratories. In total, the expanded surveillance and investigation identified 7 confirmed autochthonous cases; 3 presented with meningoencephalitis and 4 with flu-like syndrome. Symptoms began between August 14 and 30, 2003. All resided in or had stayed around Fréjus during August 2003. The number of human cases remained limited in time and space. No other cases were identified outside the Var department, despite the expansion of surveillance to other departments along the Mediterranean coast and a fairly high level of participation from healthcare facilities. Coordination with other surveillance components supplemented these findings. In equines, recent VWN circulation was confirmed around the equine case in the Var. The avian component detected nothing, and none of the captured mosquitoes tested positive. Initial seroprevalence results from blood donors suggest a low level of viral circulation throughout the Southern subregion. In 2004, surveillance was extended to the Mediterranean arc. (R.A.)