The first outbreak of St. Louis encephalitis (SLE) in Arkansas occurred in Pine Bluff (Jefferson County) during July-August 1991. Cases of SLE were identified mainly through reporting by physicians in Jefferson and surrounding counties. In addition, testing of stored cerebrospinal fluid specimens, a hospital chart review, and a serosurvey were performed in Pine Bluff. Twenty-eight Arkansas residents, five of whom died, had cases of SLE. Half the case patients were over age 60, and nearly half had hypertension. The serosurvey confirmed that infection with the SLE virus was not new to Pine Bluff, and that most infections in 1991 were asymptomatic. Arkansas physicians may see more cases of SLE in 1992. SLE epidemiology, clinical presentation, diagnosis, and preventive measures are reviewed.