Barriers to dissemination of Middle American epizootic hemagglutination inhibition subtype I-AB, and enzootic, subtype IE, Venezuelan encephalitis (VE) viruses were examined in a colony of the enzootic vector mosquito, Culex (Melanoconion) taeniopus. This species is highly susceptible to oral infection with enzootic, but not epizootic, virus strains. Adult female mosquitoes were intrathoracically inoculated with epizootic virus suspensions to ascertain whether a mesenteron infection barrier exists to these subtype I-AB strains. All inoculated mosquitoes became infected, including those receiving only 10 chick embryo cell culture plaque-forming units (CEC pfu). This confirmed that a mesenteron infection barrier exists to epizootic, but not enzootic Middle American VE strains. Mosquitoes were also given high titer hamster bloodmeals of epizootic viruses and dissected at 2-day intervals to determine the location of virus in the few infected individuals. With mean bloodmeal titers of up to 105.3 CEC pfu, only 20% or less of the mosquitoes became infected, and virus replication was confined to the mesenteron. This indicated that a mesenteron escape barrier to epizootic VE viruses exists in this mosquito. Mosquitoes were also given large and small oral doses of enzootic virus strains to compare viral replication patterns. With high titer bloodmeals, virus disseminated from the mesenteron within 4 days of infection, and titers in mosquitoes peaked 7–9 days after infection. All mosquitoes that ingested large doses became infected. Mosquitoes receiving small oral doses of enzootic viruses showed a different pattern of virus replication. Over 90% of mosquitoes engorging bloodmeal titers of 100.7 CEC pfu became infected, but the virus failed to escape from, or was delayed in disseminating beyond, the mesenteron. Thus, the mesenteron escape barrier also exists to enzootic strains, and appears to be inversely related to the bloodmeal titer, reaching 61% with undetectable bloodmeal titers.