The infection of chipmunks (Tamias striatus), the vertebrate host of La Crosse (LAC) arbovirus, or snowshoe hares (Lepus americanus), the host of snowshoe hare (SSH) virus, was analyzed following subcutaneous inoculation with either LAC or SSH or certain LAC-SSH reassortant viruses. After inoculation, no adult hares or chipmunks developed signs of illness. Another reassortant, genotype LAC/LAC/SSH, has exhibited a marked inability to infect chipmunks and was avirulent for mice, probably because of a mutation in its L RNA segment. In chipmunks inoculated with reassortant viruses, neither the durations of viremias nor the maximum titers attained were demonstrably different from those found after inoculation with the parent LAC or SSH viruses. However, viruses with a SSH M RNA induced a higher viremia in snowshoe hares than viruses with a LAC M RNA. Also, the amount of virus needed to produce a detectable infection of chipmunks or hares was lower for viruses in which the M RNA came from the SSH parent than for those viruses having a LAC M RNA. Convalescent phase chipmunk and hare sera from animals infected with SSH virus or reassortant viruses having a SSH M RNA, neutralized parental SSH virus more effectively than did LAC virus. Conversely, the sera of animals infected with LAC virus or reassortants having a LAC M RNA, neutralized LAC virus more efficiently than did SSH virus.