To a mouse hepatitis virus strain MHV-S, 4 week-old ICR mice were shown to be fully resistant irrespective of route and dose of inoculation, and fatal infection was produced only with cortisone treatment. Two-week-old mice also showed high resistance to MHV-S except for after intracerebral inoculation, and 60% of infected mice died. Mice aged 1 week or less, however, died after intracerebral, intraperitoneal, subcutaneous and intranasal inoculation, while some of them survived after peroral inoculation. Between mice aged 4 weeks and those aged 1 week or less, there was a significant difference in viral growth in the liver after intranasal inoculation, whereas almost the same degree of viral multiplication was seen in the brain of both age groups. Such age-dependent difference in susceptibility to a low-virulent mouse hepatitis virus especially after nasal inoculation is discussed in relation to natural infection in mouse breeding colonies.