The spatial and temporal distribution of LaCrosse encephalitis cases in Illinois was analyzed using a geographic information system (GIS) and spatial statistics. Case data were obtained from the Illinois Department of Public Health and mapped on the county, town, and address level. Human cases were concentrated in and around the city of Peoria in central Illinois. Local spatial statistics were used to identify hot spots where cases appear to be concentrated in the Peoria region. Several small towns surrounding the city of Peoria appeared as foci where cases were most common. Second-order spatial analysis of the case distribution was conducted on the address level. Cases were clustered within a range of 3.0 km in the city of Peoria. Since most cases appear to be associated with residential (peridomestic) exposure, and since several cases have been reported from neighboring addresses, transmission may be concentrated around specific sites (hardwood ravines, tire piles). The GIS and spatial analysis may be useful in identifying and targeting for intervention potential sites of enzootic transmission.