An epidemic of St. Louis encephalitis (SLE) occurred in Memphis-Shelby County, Tennessee, in the summer of 1975, as part of an outbreak involving large portions of the Eastern United States. A total of 187 suspected cases were reported, of which 62 were laboratory-confirmed or presumptive SLE. The overall attack rate was 8.1/100,000; rates were higher in lower socioeconomic districts. The case fatality rate was 19.4%. Climatologic data and related factors favoring the occurrence of this outbreak are discussed.