In weanling Swiss Webster mice, the LD 50 and ID 50 are similar, indicating that most infections lead to a lethal outcome at this age. LACV first replicates in tissues near the inoculation site, enters the blood stream, infects the nasal turbinates, and gains access to the CNS, presumably via olfactory neurons. This model will be useful to identify attenuated vaccine candidates that are deficient in the ability to disseminate from the site of inoculation, to replicate to high titers in the nasal turbinates, or to establish infection in mouse CNS. The CNS infection of mice appears more widespread than described for human infection, both in the brain and spinal cord. LACV is highly infectious both by the IP and IN routes suggesting that infection of natural mammalian hosts such as the chipmunk or squirrel might occur by the oral/intranasal route in addition to the bite of an infected mosquito. In rhesus monkeys, LACV is highly infectious with as little as 10 PFU resulting in the development of neutralizing antibodies, but clinical disease is not observed at any dose tested, suggesting that rhesus monkeys will be useful for studying the infectivity and immunogenicity of live attenuated virus vaccine candidates, but will be of limited usefulness for the evaluation of their level of attenuation.