In 1980 Reeves wrote that epidemics of St. Louis encephalitis (SLE) are preventable by means of surveillance and vector abatement. This view is examined in the light of epidemic activity during the last decade (1977–1986), in which 9 discrete outbreaks occurred. In addition, 5 interactive factors (virus, vector, viremic host, human immunity, environmental temperature) described by Reeves as essential to the development of an SLE epidemic are reviewed in the light of recent research. Although much progress has been achieved, many questions remain about SLE epidemiology and ecology. Among the most important are: Do Culex pipiens complex mosquitoes play a significant role in SLE virus transmission in the western United States? Is there a sylvatic cycle of SLE virus transmission in the east-central United States? What are the most sensitive and specific predictors of SLE virus activity in the east-central United States? What are the overwintering mechanisms which assure SLE virus recrudescence, and what role does transovarial transmission of virus play?