West Nile virus is a novel pathogen in the United States, the agent of an emerging infectious disease which poses a significant public health threat in its own right and also underscores the need for a more thorough and updated understanding of the ecology and transmission of arboviruses in general. Mosquito collections were performed in St. Joseph County, Indiana in 2003-2006, the four years immediately following the initial epidemic of West Nile virus infection in Indiana, and the results were combined with historical data to provide an updated summary of the mosquito fauna of the region. An illustrated guide to morphological identification of all reported species from the five-state region surrounding and including Indiana was produced, including information of interest to public health professionals and researchers. Mosquitoes collected during the four-year survey were tested for infection with West Nile virus, and virus was detected in a total of 15 pools of mosquitoes, including nine pools of Cx. pipiens, five pools of mixed or undifferentiated Cx. pipiens and Cx. restuans, and one pool of Aedes triseriatus. Viral RNA was isolated from the brains of dead birds collected in the county during periods of viral transmission, and sequence information from this RNA was analyzed to infer relationships among local viral isolates and those made elsewhere in North America over the course of several years. The results of this analysis suggest that the rate of overwinter survival of individual strains of virus in cold-winter areas is very low, while the rate of transportation of novel strains of virus over large geographic distances is relatively high. The data presented are consistent with the long-standing hypothesis of long-distance rapid transportation of West Nile virus by migratory birds.