A small, focal outbreak of St. Louis encephalitis (SLE) in humans occurred during September 1979 in the vicinity of Greenville, Mississippi. Excellent correlation was demonstrated between the occurrence of human cases and the prevalence of SLE antibody in house sparrows collected in October 1979. At the geographic focal point of the outbreak where 11 cases were documented, the prevalence of SLE neutralizing antibody in house sparrows was 44.6%. Antibody prevalence in the birds decreased with distance from the focus of human cases and was lowest in locations without recognized human disease. Little or no serologic evidence was found for SLE virus transmission in Memphis, Tennessee, or in southern (coastal) counties of Mississippi. Results provide additional documentation for the usefulness of monitoring SLE antibody prevalence in house sparrows as an indication of the level of SLE virus transmission but emphasize the focal nature of viral activity.