Serologically negative birds and mammals of species, known from other studies to be exposed naturally to St. Louis encephalitis (SLE) virus in Memphis, Tennessee, and other selected species were inoculated experimentally with strains of SLE virus to determine their potential as natural hosts. Mosquitoes (Culex sp.) were allowed to feed on some of the inoculated vertebrate species, held for 14 days, and tested for SLE infection. The cardinals (Richmondena cardinalis), robins (Turdus migratorius), and baby chicks (Gallus gallus) all became viremic; 97% of the bobwhites (Colinus virginianus) and 20% of the Japanese quail (Coturnix coturnix) became viremic. No viremia was detected in raccoons (Procyon lotor), opossums (Didelphis virginiana), or adult cotton rats (Sigmodon hispidus). Only 20% of cottontail rabbits (Sylvilagus audubonii), 50% of wood rats (Neotoma mexicana), and 75% of hamsters (Mesocricetus auratus) but all the young cotton rats and least chipmunks (Eutamias minimus) were susceptible. Robins had the highest titered viremia but were viremic for the shortest period of time. Bobwhites had lower peak viremia titers but for a longer duration. Biologic differences in the response of some vertebrates to different SLE strains were noted. Culex pipiens quinquefasciatus mosquitoes readily became infected after feeding on viremic cardinals. Comparisons of the experimental data with information obtained from field investigations provided a better understanding of the contributions of the various vertebrate species to the transmission and maintenance of SLE virus in nature.