During the 1971 epidemic of Venezuelan equine encephalomyelitis (VEE) in south Texas, 203 suspect VEE cases were evaluated by the Center for Disease Control. Sixty-seven were confirmed as cases of VEE. Laboratory confirmation was accomplished by isolation of VEE virus from a serum specimen taken during the acute illness in 50 (75%) of the confirmed cases. Serological confirmation was obtained in 17 cases (25%). Virus isolations were most often obtained from sera collected during the first 3 days of illness. Peak serum virus titers (algebraic mean, 10(5-7) suckling mouse intracranial 50% lethal doses [SMICLD50] per ml) occurred on day 2 of illness. One-half of the sera from which virus was isolated contained at least 10(5) SMICLD50/ml, which has been shown to be sufficient to infect some vector mosquitoes. Blood from 13 virus-positive VEE cases was obtained 1 and 11 months after illness. Hemagglutination-inhibiting, complement-fixing, and neutralizing antibodies were formed by all 13 patients 1 month after illness. Hemagglutination-inhibiting antibody titers were essentially unchanged 11 months after illness. Complement-fixing antibody was undetectable 11 months after illness in 23% of cases and was detectable at dilutions of 1:8 or 1:6 in 77%. Neutralizing antibody (measured by log neutralization index) was not detectable 1 year after illness in one person (8%); titers had declined from 1.0 to 2.0 in 46%, were unchanged in 39%, and were not tested in one person (8%). No evidence of intrafamilial spread of VEE virus was obtained in either of two illness and antibody surveys. A randomized household illness and antibody survey of 681 Port Isabel residents revealed an inapparent infection ratio of 1:11 and an overall antibody prevalence of 3.2%.