From 8 August through 5 December 1977, 110 laboratory-documented cases (78 confirmed, 32 presumptive) of St. Louis encephalitis (SLE) occurred in 20 counties throughout central-south Florida. Most cases were initially identified through an active surveillance system involving repeated contact of hospital infection control officers. This outbreak had three characteristics that are unusual for SLE epidemics in the eastern United States: it lacked an urban focus, a disproportionate number of cases affected young males, and the epidemic period extended into December. There was no significant difference between attack rates for blacks and whites. Males were significantly more often affected than females. Because of the time required for laboratory confirmation of cases, most outbreak control measures were initiated after the outbreak was declining. Reporting of clinically suspected SLE cases to initiate epidemic mosquito control should improve the timeliness of control measures in future outbreaks.