West Nile virus (WNV) was first detected in Louisiana during August of 2001. An outbreak of 204 human cases of neuro-invasive disease (NID) and 25 deaths occurred in 2002. In the 2 years following, lower numbers of human cases were identified (101 NID cases in 2003 and 84 in 2004) but intense localized foci were observed. The incidence of NID has been particularly high in the elderly (65 years and older). The distribution of West Nile cases has consisted of sporadic cases with a few very intense foci. Annually, human cases have occurred from June through December, with a peak number of new cases in August. As compared with other WNV serosurveys conducted in the United States, it appears that the WNV seroprevalence in Louisiana is not elevated.