As the geographic range of reported human West Nile virus (WNV) disease has expanded across the United States, seasonal transmission and outbreaks have persisted over several years in many areas of the country. West Nile virus neuroinvasive disease (WNND) case reports from 2002 to 2006 were reviewed to determine which areas of the country have the highest reported cumulative incidence and whether those areas have had consistently high annual incidence. During the 5-year period examined, 9632 cases of WNND were reported nationwide. The cumulative incidence of WNND ranged from 0.2 to 32.2 per 100,000 population by state and from 0.1 to 241.2 per 100,000 population by county. States and counties with the highest cumulative incidence were primarily located in the northern Great Plains. States with consistently high annual incidence included South Dakota, North Dakota, Wyoming, New Mexico, Mississippi, Nebraska, Louisiana, and Colorado. All of these states, with the exception of New Mexico, were also among the states with the highest cumulative incidence. Counties with repeatedly high annual incidence were also primarily in the Great Plains and mid-South. The risk of WNND appears to be highest in areas where the primary WNV vectors are Culex tarsalis and Cx. quinquefasciatus mosquitoes.