This study was performed to examine mouse age-dependent changes in susceptibility to MHV-2-CC-infection and participation of macrophages in such changes in BALB/c mice. One-week-old mice were fully susceptible (mortality, 100%), 2-week-old semi-susceptible (36%), and 3- and 4-week-old fully resistant (0%) to MHV-2-CC, respectively. Such age-dependent differences corresponded well with the differences in the virus titers in the liver, spleen and blood and in the severity of liver lesions. In 1-week-old mice with peritoneal exudate cells (PEC) transferred from 4-week-old mice and infected with MHV-2-CC, a slight prolongation of survival time was recorded, although there was no difference in mortality. In 3-week-old mice infected with MHV-2-CC after silica-treatment to suppress macrophages, there was no significant change in susceptibility. In macrophages infected with MHV-2-CC in vitro, the virus replicated better in macrophages obtained from younger mice. These results suggest that macrophages may play a small role in the age-related development of resistance to MHV-2-CC infection in BALB/c mice.