In the latter half of the 1900s, St. Louis encephalitis (SLE) became the predominant mosquito-borne disease of man in Florida and was responsible for recurring epidemics in the south and central portions of the state. Major epidemics occurred in 1959, 1961, 1962, 1977, and 1990 and 1997. The 1959-1962 outbreaks in the Tampa Bay area involved 55 fatalities amongst 315 cases. In contrast the most recent epidemic (1997) yielded 9 cases throughout the state, with only one fatality. The 1990 epidemic was largest (223 documented cases) and most widespread (cases in 28 counties), with 11 fatalities. The 1990 epidemic was first recognized in Indian River County, which also experienced the highest impact of any affected county (19 confirmed cases and one fatality, despite a relatively low population).

Most people infected with SLEV experience mild symptoms, if any. A smaller group may experience more severe symptoms (including fever) and require medical assistance. The most affected people display neuroinvasive symptoms such as encephalitis or paralysis and are at risk of death. SLEV is normally associated with wild birds and several species of mosquito, most notably Culex nigripalpus in south and central Florida.