As an initial step in development of a live attenuated LACV vaccine, we sought to better characterize LACV infection in weanling mice because at this age mice can be used to evaluate both the level of attenuation and immunogenicity of candidate vaccine viruses. Previous LACV pathogenesis studies in suckling mice inoculated subcutaneously with a mosquito isolate of LACV demonstrated that viral antigen was detected in the cytoplasm of striated muscles, the interscapular brown fat, and the endothelial and smooth muscle cells of small arteries and veins [28] . When virus was first detected in the brain, it was confined to cerebral vascular endothelial cells but later spread to neurons. The authors suggest that the late infection of the dorsal route ganglion indicates that the virus does not penetrate the CNS via nerves but rather by vascular endothelial cells [28] . This previous model therefore suggests that virus first replicates in muscle cells leading to the development of viremia with subsequent hematogenous spread to the CNS, and we sought in the present study to examine if this pattern of infection also occurred in weanling mice. In weanling mice inoculated intraperitoneally with 1 or 100 LD 50 of LACV, virus was first detected on days 1 -3 in tissues near the inoculation site. At either dose, virus was no longer detectable by days 4 and 5 in these tissues, suggesting that it was rapidly cleared by the innate immune system. Interestingly, the virus was not detected in muscle tissue until day 3 post inoculation and clearly did not preferentially infect this tissue. Rather, outside the CNS, the virus replicated to highest titers in the nasal turbinates and appears to spread from this site into the brain. Immunohistochemical staining of the nasal turbinate tissue was not sensitive enough to identify the LACV infected cells, but is thought LACV may gain access to the CNS via cells in the nasal turbinates. This suggestion is offered with the caveat that respiratory epithelial cells could also have been infected, but the magnitude of the infection could not be detected with the IHC staining. To travel from the nasal olfactory epithelium to the olfactory bulb, the virus a Days with significant number of monkeys 1 SD from the pre-inoculation mean (day -7 and 0 combined) are boxed (chi square, p < 0.05, n = 16), mean values displayed. b Abbreviations: MCV-mean corpuscular volume, MCH-mean corpuscular hemoglobin, MCHC-mean corpuscular hemoglobin concentrations, ASTaspartate aminotransferase, ALT-alanine aminotransferase, ALP-alkaline phosphatase, BUN-blood urea nitrogen. c Pre-inoculation mean determined from samples collected on days -7 and 0 post inoculation.