To identify key steps in pathogenesis of LACV in weanling mice, we evaluated LACV tissue tropism after peripheral inoculation of wild-type virus and sought to identify tissues in which virus replicated efficiently. Weanling Swiss Webster mice (21-23 days-old) were inoculated intraperitoneally with 1 or 100 LD 50 (2.5 or 4.5 log 10 PFU) of LACV/human/1960, and the tissues indicated in Figures 1  and 2 were collected from 3 mice per day on days 1-6 post inoculation. Following inoculation of either dose, virus could first be detected in tissue near the inoculation site such as inguinal lymph nodes, spleen, and ovaries/uterus. Virus was detected in serum on days 1-3, but rarely on subsequent days even in moribund mice. By day three, virus distribution was widespread and could be found in the majority of tissues sampled, albeit at very low levels with titers rarely exceeding those found in serum. The highest virus titers detected were present in nasal turbinates, brain, and spinal cord. Respiratory tissue, including lung and nasal turbinates, contained virus following inoculation with 100 or 1 LD 50 beginning on days 1 and 2, respectively. CNS infection appeared to follow respira-Tissue distribution of La Crosse virus following intraperitoneal (IP) inoculation of Swiss Webster mice with 10 2.5 PFU Figure 1 Tissue distribution of La Crosse virus following intraperitoneal (IP) inoculation of Swiss Webster mice with 10 2.5 PFU. a Percent of mice positive by plaque assay represented by shading: 100% black, 66% dark gray, 33% light gray, 0% no data entry. Mean virus titer calculated only for virus positive tissues. Areas left blank indicate virus titer below detection limit of 0.7 log10 PFU/tissue. tory tissue infection, with virus being present in the brain 5 days after infection with 1 LD 50 and on day 2 after infection with 100 LD 50 . At either virus dose, infection appears early in the lymph nodes and major organs, with subsequent infection of the upper respiratory tract (nasal turbinates) followed by infection of the brain and eventually the spinal cord. By day six, mice began to succumb to infection in the high dose group showing signs of paralysis whereas mice in the low dose group failed to show clinical signs at this time, but would have succumbed later in infection. These results indicate that LACV replicates to low to moderate levels in peripheral tissues in weanling mice, with the nasal turbinates rather than striated muscle being the major site of replication.