Venezuelan equine encephalitis (VEE) virus infection of man was studied at two enzootic sites of virus activity in south Florida between 1969 and 1972. Of 181 persons bled, 20 (9%) were found to have hemagglutination-inhibition (HI) antibody ≥1/10. Antibody was found more frequently in residents than in transients (P < .02), and somewhat more frequently in males (difference not significant; P > .05). Five persons had rises in HI antibody titers during the study period. Only one of these persons had had a recent mild illness with generalized symptoms. Seven new arrivals were found to have HI antibody within 2 to 8 months of residence at an enzootic site, but were all asymptomatic. These individuals are contrasted to three previously reported persons infected outside the enzootic area who developed classic encephalitis and required hospitalization. Whether the difference in clinical response to VEE virus infection is due to variation in host susceptibility or in virulence of infecting virus strain, or both, is not known.